TDMS Study 88122-06 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus ELMIRON DATE: 06/12/01
EXPERIMENT: 88122 TEST: 06 TIME: 09:23:07
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1
CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: C88122
PATHOLOGIST: RYAN, MICHAEL CAS: 37319-17-8
------------------------------------------------------------------------------------------------------------------------------------
FINAL#1
REASONS FOR REMOVAL: ALL
REMOVAL DATE RANGE: ALL
TREATMENT GROUPS: INCLUDE ALL
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10
LAB: Battelle Columbus ELMIRON DATE: 06/12/01
EXPERIMENT: 88122 TEST: 06 TIME: 09:23:07
TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE
CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: C88122
PATHOLOGIST: RYAN, MICHAEL CAS: 37319-17-8
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF ELMIRON
===============================================================
Male Rats
------------
Organ Morphology
----- ----------
Intestine Large, Rectum Infiltration Cellular Histiocyte
Inflammation Chronic
Myxomatous Change
Liver Basophilic Focus
Eosinophilic Focus
Mixed Cell Focus
Liver: Bile Duct Hyperplasia
Lung: Alveolar Epithelium Hyperplasia
Metaplasia
Lung: Alveolus Inflammation Chronic Focal
Lymph Node, Mesenteric Infiltration Cellular Histiocyte
Inflammation Granulomatous
Mammary Gland Hyperplasia
Mammary Gland: Duct Dilatation
Pituitary Gland Hyperplasia
Preputial Gland Inflammation Chronic
Spleen Hyperplasia Lymphohistiocytic
Testes: Interstitial Cell Hyperplasia
Thyroid Gland: C-Cell Hyperplasia
Trachea Inflammation Chronic
===============================================================
Female Rats
------------
Organ Morphology
----- ----------
Heart: Myocardium Degeneration
Intestine Large, Rectum Infiltration Cellular Histiocyte
Myxomatous Change
Liver Inflammation Granulomatous
Mixed Cell Focus
Lung Congestion
Lung: Alveolus Inflammation Chronic Focal
Lymph Node, Mesenteric Infiltration Cellular Histiocyte
Mammary Gland: Duct Dilatation
Mesentery: Fat Necrosis
Spleen Hyperplasia Lymphohistiocytic
Stomach, Glandular Ulcer
===============================================================
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 1
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Adrenal Cortex |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 14/50 (28%) 16/50 (32%) 17/50 (34%) 17/50 (34%) |20/50 (40%) 17/50 (34%) 17/50 (34%) 19/50 (38%) |
|POLY-3 RATE (b) | 14/41.37 16/43.03 17/42.96 17/41.46 |20/44.10 17/43.11 17/42.90 19/40.19 |
|POLY-3 PERCENT (g) | 33.8% 37.2% 39.6% 41.0% |45.4% 39.4% 39.6% 47.3% |
|TERMINAL (d) | 13/26 (50%) 11/29 (38%) 9/25 (36%) 10/28 (36%) |14/30 (47%) 16/31 (52%) 11/28 (39%) 14/27 (52%) |
|FIRST INCIDENCE | 686 577 484 622 |462 670 474 624 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.376 P=0.545 P=0.285 P=0.406 |P=0.338 P=0.296N P=0.423N P=0.515 |
|POLY 3 | P=0.317 P=0.462 P=0.373 P=0.326 |P=0.376 P=0.364N P=0.372N P=0.517 |
|POLY 1.5 | P=0.303 P=0.428 P=0.362 P=0.301 |P=0.403 P=0.353N P=0.361N P=0.547 |
|POLY 6 | P=0.360 P=0.520 P=0.388 P=0.385 |P=0.361 P=0.381N P=0.387N P=0.495 |
|LOGISTIC REGRESSION| P=0.297 P=0.475 P=0.289 P=0.318 |P=0.389 P=0.299N P=0.350N P=0.567 |
|COCH-ARM / FISHERS | P=0.348 P=0.414 P=0.333 P=0.333 |P=0.521 P=0.339N P=0.339N P=0.500N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 3/40.43 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 7.4% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 2/25 (8%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- 561 --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.640N (e) P=0.119 (e) |(e) (e) (e) (e) |
|POLY 3 | P=0.665N (e) P=0.114 (e) |(e) (e) (e) (e) |
|POLY 1.5 | P=0.665N (e) P=0.118 (e) |(e) (e) (e) (e) |
|POLY 6 | P=0.661N (e) P=0.110 (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.651N (e) P=0.120 (e) |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.646N (e) P=0.121 (e) |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 2
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia Diffuse |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.53 0/41.91 0/39.89 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 640 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.239N P=0.220N P=0.256N P=0.229N |(e) (e) (e) (e) |
|POLY 3 | P=0.239N P=0.235N P=0.246N P=0.245N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.237N P=0.238N P=0.240N P=0.246N |(e) (e) (e) (e) |
|POLY 6 | P=0.241N P=0.230N P=0.254N P=0.242N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.242N P=0.237N P=0.240N P=0.243N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.238N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Adrenal Medulla |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 10/50 (20%) 17/50 (34%) 12/50 (24%) 13/50 (26%) |5/50 (10%) 2/50 (4%) 4/50 (8%) 4/50 (8%) |
|POLY-3 RATE (b) | 10/42.22 17/43.67 12/42.54 13/40.50 |5/41.94 2/42.89 4/41.69 4/39.41 |
|POLY-3 PERCENT (g) | 23.7% 38.9% 28.2% 32.1% |11.9% 4.7% 9.6% 10.2% |
|TERMINAL (d) | 3/26 (12%) 8/29 (28%) 5/25 (20%) 10/28 (36%) |5/30 (17%) 2/31 (7%) 3/28 (11%) 3/27 (11%) |
|FIRST INCIDENCE | 589 478 526 661 |728 (T) 728 (T) 667 706 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.537 P=0.160 P=0.349 P=0.363 |P=0.479 P=0.200N P=0.537N P=0.566N |
|POLY 3 | P=0.464 P=0.096 P=0.410 P=0.270 |P=0.504 P=0.206N P=0.504N P=0.539N |
|POLY 1.5 | P=0.472 P=0.087 P=0.414 P=0.272 |P=0.512 P=0.211N P=0.504N P=0.535N |
|POLY 6 | P=0.465 P=0.112 P=0.402 P=0.278 |P=0.500 P=0.200N P=0.503N P=0.539N |
|LOGISTIC REGRESSION| P=0.493 P=0.090 P=0.396 P=0.299 |P=0.494 P=0.200N P=0.517N P=0.554N |
|COCH-ARM / FISHERS | P=0.537 P=0.088 P=0.405 P=0.318 |P=0.554 P=0.218N P=0.500N P=0.500N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 3
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Bone |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.30 0/41.91 0/39.89 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 707 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.242N P=0.218N P=0.263N P=0.232N |(e) (e) (e) (e) |
|POLY 3 | P=0.239N P=0.233N P=0.244N P=0.244N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.238N P=0.237N P=0.240N P=0.245N |(e) (e) (e) (e) |
|POLY 6 | P=0.242N P=0.228N P=0.252N P=0.239N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.243N P=0.225N P=0.257N P=0.237N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.238N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Bone Marrow |
| Fibrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.93 1/42.42 0/39.89 1/40.22 |0/41.94 1/43.55 1/41.74 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 2.4% 0.0% 2.5% |0.0% 2.3% 2.4% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 589 574 --- 679 |--- 510 653 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.497N P=0.488N P=0.257N P=0.494N |P=0.553N P=0.509 P=0.516 (e) |
|POLY 3 | P=0.507N P=0.496N P=0.248N P=0.515N |P=0.557N P=0.508 P=0.499 (e) |
|POLY 1.5 | P=0.506N P=0.500N P=0.242N P=0.515N |P=0.555N P=0.504 P=0.499 (e) |
|POLY 6 | P=0.507N P=0.489N P=0.258N P=0.510N |P=0.557N P=0.511 P=0.499 (e) |
|LOGISTIC REGRESSION| P=0.482N P=0.492N P=0.242N P=0.494N |P=0.492N P=0.495 P=0.502 (e) |
|COCH-ARM / FISHERS | P=0.500N P=0.500N P=0.247N P=0.500N |P=0.541N P=0.500 P=0.500 (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 4
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Brain |
| Hydrocephalus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 7/50 (14%) 9/50 (18%) 6/50 (12%) |8/50 (16%) 6/50 (12%) 8/50 (16%) 10/50 (20%) |
|POLY-3 RATE (b) | 8/44.28 7/43.22 9/42.28 6/40.79 |8/43.60 6/43.12 8/42.16 10/40.85 |
|POLY-3 PERCENT (g) | 18.1% 16.2% 21.3% 14.7% |18.4% 13.9% 19.0% 24.5% |
|TERMINAL (d) | 2/26 (8%) 3/29 (10%) 3/25 (12%) 3/28 (11%) |2/30 (7%) 4/31 (13%) 3/28 (11%) 5/27 (19%) |
|FIRST INCIDENCE | 503 478 462 629 |462 678 667 525 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.375N P=0.458N P=0.459 P=0.390N |P=0.173 P=0.377N P=0.562 P=0.326 |
|POLY 3 | P=0.423N P=0.521N P=0.458 P=0.451N |P=0.189 P=0.394N P=0.580 P=0.337 |
|POLY 1.5 | P=0.411N P=0.519N P=0.481 P=0.440N |P=0.194 P=0.392N P=0.588 P=0.344 |
|POLY 6 | P=0.427N P=0.516N P=0.429 P=0.452N |P=0.189 P=0.398N P=0.571 P=0.335 |
|LOGISTIC REGRESSION| P=0.342N P=0.493N P=0.495 P=0.373N |P=0.196 P=0.381N P=0.603 P=0.371 |
|COCH-ARM / FISHERS | P=0.356N P=0.500N P=0.500 P=0.387N |P=0.236 P=0.387N P=0.607N P=0.398 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Brain: Hypothalamus |
| Compression |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 2/50 (4%) 5/50 (10%) 4/50 (8%) |5/50 (10%) 3/50 (6%) 5/50 (10%) 8/50 (16%) |
|POLY-3 RATE (b) | 6/44.12 2/42.72 5/41.39 4/40.79 |5/43.14 3/43.12 5/42.01 8/40.65 |
|POLY-3 PERCENT (g) | 13.6% 4.7% 12.1% 9.8% |11.6% 7.0% 11.9% 19.7% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 1/25 (4%) 1/28 (4%) |0/30 (0%) 1/31 (3%) 1/28 (4%) 4/27 (15%) |
|FIRST INCIDENCE | 503 478 462 629 |462 678 667 525 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.544N P=0.137N P=0.534N P=0.385N |P=0.080 P=0.348N P=0.599 P=0.232 |
|POLY 3 | P=0.561N P=0.143N P=0.545N P=0.419N |P=0.085 P=0.356N P=0.614 P=0.236 |
|POLY 1.5 | P=0.555N P=0.142N P=0.521N P=0.412N |P=0.088 P=0.357N P=0.618 P=0.240 |
|POLY 6 | P=0.560N P=0.142N P=0.575N P=0.418N |P=0.085 P=0.355N P=0.610 P=0.236 |
|LOGISTIC REGRESSION| P=0.471N P=0.114N P=0.522N P=0.331N |P=0.093 P=0.357N P=0.629 P=0.263 |
|COCH-ARM / FISHERS | P=0.522N P=0.134N P=0.500N P=0.370N |P=0.108 P=0.357N P=0.630N P=0.277 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 5
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |4/50 (8%) 4/50 (8%) 4/50 (8%) 3/49 (6%) |
|POLY-3 RATE (b) | |4/42.15 4/43.28 4/41.63 3/38.59 |
|POLY-3 PERCENT (g) | |9.5% 9.2% 9.6% 7.8% |
|TERMINAL (d) | |3/30 (10%) 2/31 (7%) 3/28 (11%) 2/26 (8%) |
|FIRST INCIDENCE | |673 677 685 656 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.504N P=0.617N P=0.610 P=0.564N |
|POLY 3 | |P=0.478N P=0.629N P=0.637 P=0.548N |
|POLY 1.5 | |P=0.470N P=0.635N P=0.638 P=0.544N |
|POLY 6 | |P=0.483N P=0.621N P=0.635 P=0.550N |
|LOGISTIC REGRESSION| |P=0.481N P=0.630N P=0.635 P=0.550N |
|COCH-ARM / FISHERS | |P=0.429N P=0.643N P=0.643N P=0.511N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |5/50 (10%) 3/50 (6%) 2/50 (4%) 3/49 (6%) |
|POLY-3 RATE (b) | |5/42.39 3/43.14 2/41.46 3/38.69 |
|POLY-3 PERCENT (g) | |11.8% 7.0% 4.8% 7.8% |
|TERMINAL (d) | |4/30 (13%) 1/31 (3%) 2/28 (7%) 2/26 (8%) |
|FIRST INCIDENCE | |596 678 728 (T) 624 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.472N P=0.342N P=0.243N P=0.424N |
|POLY 3 | |P=0.443N P=0.346N P=0.224N P=0.407N |
|POLY 1.5 | |P=0.437N P=0.351N P=0.222N P=0.402N |
|POLY 6 | |P=0.447N P=0.340N P=0.228N P=0.408N |
|LOGISTIC REGRESSION| |P=0.450N P=0.345N P=0.221N P=0.402N |
|COCH-ARM / FISHERS | |P=0.406N P=0.357N P=0.218N P=0.369N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 6
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |1/50 (2%) 0/50 (0%) 1/50 (2%) 2/49 (4%) |
|POLY-3 RATE (b) | |1/41.94 0/42.89 1/41.46 2/38.32 |
|POLY-3 PERCENT (g) | |2.4% 0.0% 2.4% 5.2% |
|TERMINAL (d) | |1/30 (3%) 0/31 (0%) 1/28 (4%) 2/26 (8%) |
|FIRST INCIDENCE | |728 (T) --- 728 (T) 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.191 P=0.493N P=0.747 P=0.450 |
|POLY 3 | |P=0.207 P=0.496N P=0.758 P=0.469 |
|POLY 1.5 | |P=0.211 P=0.498N P=0.759 P=0.472 |
|POLY 6 | |P=0.204 P=0.493N P=0.758 P=0.467 |
|LOGISTIC REGRESSION| |P=0.191 (e) P=0.747 P=0.450 |
|COCH-ARM / FISHERS | |P=0.229 P=0.500N P=0.753N P=0.492 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Clitoral Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |7/50 (14%) 10/50 (20%) 11/50 (22%) 8/49 (16%) |
|POLY-3 RATE (b) | |7/42.42 10/43.59 11/42.41 8/38.80 |
|POLY-3 PERCENT (g) | |16.5% 22.9% 25.9% 20.6% |
|TERMINAL (d) | |5/30 (17%) 6/31 (19%) 7/28 (25%) 7/26 (27%) |
|FIRST INCIDENCE | |651 653 491 588 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.464 P=0.334 P=0.190 P=0.396 |
|POLY 3 | |P=0.492 P=0.316 P=0.212 P=0.424 |
|POLY 1.5 | |P=0.507 P=0.307 P=0.212 P=0.432 |
|POLY 6 | |P=0.478 P=0.329 P=0.208 P=0.419 |
|LOGISTIC REGRESSION| |P=0.500 P=0.317 P=0.207 P=0.422 |
|COCH-ARM / FISHERS | |P=0.543N P=0.298 P=0.218 P=0.483 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 7
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Eye |
| Cataract |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/0 (0%) 1/1 (100%) 0/0 (0%) 1/1 (100%) |0/0 (0%) 1/3 (33%) 1/1 (100%) 2/3 (67%) |
|POLY-3 RATE (b) | 0/0.00 1/1.00 0/0.00 1/1.00 |0/0.00 1/2.96 1/1.00 2/3.00 |
|POLY-3 PERCENT (g) | 0.0% 100.0% 0.0% 100.0% |0.0% 33.8% 100.0% 66.7% |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 1/1 (100%) |0/0 (0%) 0/1 (0%) 0/0 (0%) 2/3 (67%) |
|FIRST INCIDENCE | --- 713 --- 727 (T) |--- 653 685 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.575 P=0.511 (e) P=1.000 |
|POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.178 (e) (e) P=1.000 |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.488 P=1.000 (e) P=1.000 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Eye |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/0 (0%) 0/1 (0%) 0/0 (0%) 0/1 (0%) |0/0 (0%) 2/3 (67%) 0/1 (0%) 0/3 (0%) |
|POLY-3 RATE (b) | 0/0.00 0/0.94 0/0.00 0/1.00 |0/0.00 2/2.72 0/0.83 0/3.00 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 73.5% 0.0% 0.0% |
|TERMINAL (d) | 0/0 (0%) 0/0 (0%) 0/0 (0%) 0/1 (0%) |0/0 (0%) 1/1 (100%) 0/0 (0%) 0/3 (0%) |
|FIRST INCIDENCE | --- --- --- --- |--- 719 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.149N P=0.513 (e) (e) |
|POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.051N (e) (e) (e) |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.163N P=1.000 (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 8
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Heart: Atrium |
| Thrombosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 4/50 (8%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.25 4/42.84 0/39.89 1/40.04 |0/41.94 1/43.11 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.9% 9.3% 0.0% 2.5% |0.0% 2.3% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 721 574 --- 727 (T) |--- 670 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.243N P=0.372 P=0.277N P=0.503N |P=0.605N P=0.516 (e) (e) |
|POLY 3 | P=0.233N P=0.354 P=0.244N P=0.510N |P=0.585N P=0.506 (e) (e) |
|POLY 1.5 | P=0.235N P=0.343 P=0.240N P=0.513N |P=0.586N P=0.503 (e) (e) |
|POLY 6 | P=0.227N P=0.373 P=0.251N P=0.504N |P=0.583N P=0.509 (e) (e) |
|LOGISTIC REGRESSION| P=0.237N P=0.337 P=0.262N P=0.503N |P=0.588N P=0.500 (e) (e) |
|COCH-ARM / FISHERS | P=0.228N P=0.339 P=0.247N P=0.500N |P=0.585N P=0.500 (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Heart: Myocardium |
| Degeneration |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 41/50 (82%) 41/50 (82%) 42/50 (84%) 41/50 (82%) |38/50 (76%) 30/50 (60%) 31/50 (62%) 34/50 (68%) |
|POLY-3 RATE (b) | 41/47.02 41/46.50 42/48.61 41/45.31 |38/47.00 30/44.84 31/44.50 34/46.40 |
|POLY-3 PERCENT (g) | 87.2% 88.2% 86.4% 90.5% |80.8% 66.9% 69.7% 73.3% |
|TERMINAL (d) | 25/26 (96%) 27/29 (93%) 21/25 (84%) 24/28 (86%) |23/30 (77%) 22/31 (71%) 21/28 (75%) 20/27 (74%) |
|FIRST INCIDENCE | 475 478 419 352 |427 526 375 139 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.520N P=0.335N P=0.380 P=0.465N |P=0.322 P=0.086N P=0.240N P=0.513N |
|POLY 3 | P=0.376 P=0.571 P=0.577N P=0.429 |P=0.459N P=0.090N P=0.148N P=0.261N |
|POLY 1.5 | P=0.377 P=0.551 P=0.606N P=0.421 |P=0.488N P=0.076N P=0.123N P=0.267N |
|POLY 6 | P=0.442 P=0.626 P=0.540N P=0.515 |P=0.432N P=0.110N P=0.187N P=0.260N |
|LOGISTIC REGRESSION| P=0.387 P=0.574 P=0.504 P=0.410 |P=0.470 P=0.049N* P=0.099N P=0.301N |
|COCH-ARM / FISHERS | P=0.558N P=0.602N P=0.500 P=0.602N |P=0.496N P=0.066N P=0.097N P=0.252N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 9
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Colon |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 1/50 (2%) 0/50 (0%) 3/50 (6%) |2/50 (4%) 3/50 (6%) 3/50 (6%) 3/50 (6%) |
|POLY-3 RATE (b) | 4/41.37 1/41.91 0/39.89 3/40.04 |2/41.94 3/42.94 3/41.71 3/40.32 |
|POLY-3 PERCENT (g) | 9.7% 2.4% 0.0% 7.5% |4.8% 7.0% 7.2% 7.4% |
|TERMINAL (d) | 3/26 (12%) 1/29 (3%) 0/25 (0%) 3/28 (11%) |2/30 (7%) 2/31 (7%) 1/28 (4%) 2/27 (7%) |
|FIRST INCIDENCE | 686 727 (T) --- 727 (T) |728 (T) 716 667 139 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.553 P=0.152N P=0.072N P=0.465N |P=0.437 P=0.515 P=0.478 P=0.460 |
|POLY 3 | P=0.528 P=0.174N P=0.064N P=0.518N |P=0.462 P=0.511 P=0.497 P=0.482 |
|POLY 1.5 | P=0.530 P=0.178N P=0.062N P=0.521N |P=0.467 P=0.506 P=0.497 P=0.484 |
|POLY 6 | P=0.528 P=0.167N P=0.068N P=0.509N |P=0.460 P=0.517 P=0.498 P=0.482 |
|LOGISTIC REGRESSION| P=0.529 P=0.160N P=0.073N P=0.501N |P=0.487 P=0.519 P=0.492 P=0.540 |
|COCH-ARM / FISHERS | P=0.541 P=0.181N P=0.059N P=0.500N |P=0.491 P=0.500 P=0.500 P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Erosion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/48 (0%) 0/48 (0%) 2/49 (4%) 2/45 (4%) |0/46 (0%) 0/43 (0%) 0/44 (0%) 0/42 (0%) |
|POLY-3 RATE (b) | 0/39.46 0/40.92 2/40.89 2/36.89 |0/39.83 0/38.64 0/38.77 0/36.68 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 5.4% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- 484 727 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.126 (e) P=0.240 P=0.254 |(e) (e) (e) (e) |
|POLY 3 | P=0.104 (e) P=0.245 P=0.222 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.102 (e) P=0.246 P=0.218 |(e) (e) (e) (e) |
|POLY 6 | P=0.109 (e) P=0.241 P=0.229 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.119 (e) P=0.162 P=0.254 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.109 (e) P=0.253 P=0.231 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 10
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/48 (0%) 0/48 (0%) 0/49 (0%) 4/45 (9%) |0/46 (0%) 0/43 (0%) 0/44 (0%) 18/42 (43%) |
|POLY-3 RATE (b) | 0/39.46 0/40.92 0/39.70 4/37.40 |0/39.83 0/38.64 0/38.77 18/37.53 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 10.7% |0.0% 0.0% 0.0% 48.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 12/27 (44%) |
|FIRST INCIDENCE | --- --- --- 604 |--- --- --- 588 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.002 ** (e) (e) P=0.074 |P<0.001 ** (e) (e) P<0.001 ** |
|POLY 3 | P<0.001 ** (e) (e) P=0.052 |P<0.001 ** (e) (e) P<0.001 ** |
|POLY 1.5 | P<0.001 ** (e) (e) P=0.050 |P<0.001 ** (e) (e) P<0.001 ** |
|POLY 6 | P<0.001 ** (e) (e) P=0.058 |P<0.001 ** (e) (e) P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.053 |P<0.001 ** (e) (e) P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.051 |P<0.001 ** (e) (e) P<0.001 ** |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/48 (2%) 0/48 (0%) 1/49 (2%) 5/45 (11%) |0/46 (0%) 0/43 (0%) 0/44 (0%) 1/42 (2%) |
|POLY-3 RATE (b) | 1/40.12 0/40.92 1/40.40 5/37.85 |0/39.83 0/38.64 0/38.77 1/36.77 |
|POLY-3 PERCENT (g) | 2.5% 0.0% 2.5% 13.2% |0.0% 0.0% 0.0% 2.7% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 4/28 (14%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 505 --- 484 261 |--- --- --- 706 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.007 ** P=0.509N P=0.758 P=0.111 |P=0.198 (e) (e) P=0.482 |
|POLY 3 | P=0.004 ** P=0.496N P=0.759N P=0.087 |P=0.205 (e) (e) P=0.484 |
|POLY 1.5 | P=0.004 ** P=0.498N P=0.756N P=0.083 |P=0.205 (e) (e) P=0.483 |
|POLY 6 | P=0.005 ** P=0.493N P=0.756 P=0.092 |P=0.205 (e) (e) P=0.486 |
|LOGISTIC REGRESSION| P=0.008 ** P=0.504N P=0.687 P=0.097 |P=0.204 (e) (e) P=0.483 |
|COCH-ARM / FISHERS | P=0.005 ** P=0.500N P=0.747N P=0.088 |P=0.205 (e) (e) P=0.477 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 11
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Myxomatous Change |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/48 (0%) 1/48 (2%) 3/49 (6%) 25/45 (56%) |0/46 (0%) 1/43 (2%) 12/44 (27%) 35/42 (83%) |
|POLY-3 RATE (b) | 0/39.46 1/41.22 3/40.39 25/38.85 |0/39.83 1/39.36 12/39.71 35/39.32 |
|POLY-3 PERCENT (g) | 0.0% 2.4% 7.4% 64.4% |0.0% 2.5% 30.2% 89.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 2/25 (8%) 19/28 (68%) |0/30 (0%) 0/31 (0%) 9/28 (32%) 24/27 (89%) |
|FIRST INCIDENCE | --- 645 492 261 |--- 474 483 525 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P<0.001 ** P=0.526 P=0.117 P<0.001 ** |P<0.001 ** P=0.508 P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.509 P=0.122 P<0.001 ** |P<0.001 ** P=0.498 P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.504 P=0.124 P<0.001 ** |P<0.001 ** P=0.493 P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.515 P=0.118 P<0.001 ** |P<0.001 ** P=0.503 P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.498 P=0.121 P<0.001 ** |P<0.001 ** P=0.470 P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.500 P=0.125 P<0.001 ** |P<0.001 ** P=0.483 P<0.001 ** P<0.001 ** |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Intestine Large, Rectum |
| Parasite Metazoan |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/48 (10%) 8/48 (17%) 4/49 (8%) 3/45 (7%) |2/46 (4%) 3/43 (7%) 1/44 (2%) 0/42 (0%) |
|POLY-3 RATE (b) | 5/39.46 8/41.22 4/40.39 3/36.89 |2/39.83 3/38.64 1/38.77 0/36.68 |
|POLY-3 PERCENT (g) | 12.7% 19.4% 9.9% 8.1% |5.0% 7.8% 2.6% 0.0% |
|TERMINAL (d) | 5/26 (19%) 7/29 (24%) 3/25 (12%) 3/28 (11%) |2/30 (7%) 3/31 (10%) 1/28 (4%) 0/27 (0%) |
|FIRST INCIDENCE | 727 (T) 645 492 727 (T) |728 (T) 728 (T) 728 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.141N P=0.347 P=0.524N P=0.311N |P=0.123N P=0.515 P=0.524N P=0.261N |
|POLY 3 | P=0.185N P=0.302 P=0.485N P=0.393N |P=0.115N P=0.486 P=0.509N P=0.255N |
|POLY 1.5 | P=0.193N P=0.288 P=0.480N P=0.404N |P=0.115N P=0.479 P=0.510N P=0.256N |
|POLY 6 | P=0.170N P=0.322 P=0.498N P=0.372N |P=0.114N P=0.496 P=0.509N P=0.254N |
|LOGISTIC REGRESSION| P=0.177N P=0.322 P=0.503N P=0.311N |P=0.123N P=0.515 P=0.524N (e) |
|COCH-ARM / FISHERS | P=0.182N P=0.276 P=0.487N P=0.394N |P=0.116N P=0.468 P=0.517N P=0.270N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 12
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Islets, Pancreatic |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 1/50 (2%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/41.23 1/42.41 1/39.93 2/41.38 |1/41.94 1/42.95 0/41.46 1/39.32 |
|POLY-3 PERCENT (g) | 2.4% 2.4% 2.5% 4.8% |2.4% 2.3% 0.0% 2.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |1/30 (3%) 0/31 (0%) 0/28 (0%) 1/27 (4%) |
|FIRST INCIDENCE | 724 577 716 237 |728 (T) 714 --- 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.357 P=0.754N P=0.728 P=0.499 |P=0.647 P=0.747N P=0.514N P=0.739 |
|POLY 3 | P=0.359 P=0.755N P=0.754 P=0.501 |P=0.659 P=0.756N P=0.502N P=0.746 |
|POLY 1.5 | P=0.356 P=0.759N P=0.758 P=0.496 |P=0.661 P=0.758N P=0.502N P=0.748 |
|POLY 6 | P=0.364 P=0.747N P=0.747 P=0.512 |P=0.658 P=0.753N P=0.503N P=0.746 |
|LOGISTIC REGRESSION| P=0.415 P=0.762N P=0.740 P=0.572 |P=0.655 P=0.754N (e) P=0.739 |
|COCH-ARM / FISHERS | P=0.361 P=0.753N P=0.753N P=0.500 |P=0.677 P=0.753N P=0.500N P=0.753N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Hydronephrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.46 0/41.91 0/39.89 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 685 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.247N P=0.227N P=0.272N P=0.243N |(e) (e) (e) (e) |
|POLY 3 | P=0.239N P=0.234N P=0.245N P=0.245N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.237N P=0.237N P=0.240N P=0.246N |(e) (e) (e) (e) |
|POLY 6 | P=0.241N P=0.230N P=0.254N P=0.241N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.243N P=0.235N P=0.245N P=0.243N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.238N P=0.247N P=0.247N P=0.247N |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 13
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Infarct |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 2/41.24 0/41.91 2/40.86 0/40.04 |2/42.39 0/42.89 0/41.46 1/39.32 |
|POLY-3 PERCENT (g) | 4.9% 0.0% 4.9% 0.0% |4.7% 0.0% 0.0% 2.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |1/30 (3%) 0/31 (0%) 0/28 (0%) 1/27 (4%) |
|FIRST INCIDENCE | 724 --- 582 --- |596 --- --- 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.287N P=0.230N P=0.666 P=0.246N |P=0.674N P=0.241N P=0.253N P=0.535N |
|POLY 3 | P=0.293N P=0.233N P=0.691 P=0.243N |P=0.654N P=0.234N P=0.242N P=0.526N |
|POLY 1.5 | P=0.292N P=0.237N P=0.694N P=0.245N |P=0.652N P=0.236N P=0.240N P=0.522N |
|POLY 6 | P=0.293N P=0.227N P=0.686 P=0.239N |P=0.656N P=0.233N P=0.244N P=0.529N |
|LOGISTIC REGRESSION| P=0.278N P=0.221N P=0.695 P=0.238N |P=0.658N P=0.239N P=0.237N P=0.515N |
|COCH-ARM / FISHERS | P=0.281N P=0.247N P=0.691N P=0.247N |P=0.646N P=0.247N P=0.247N P=0.500N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney |
| Nephropathy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 40/50 (80%) 42/50 (84%) 41/50 (82%) 37/50 (74%) |16/50 (32%) 13/50 (26%) 11/50 (22%) 16/50 (32%) |
|POLY-3 RATE (b) | 40/45.77 42/46.45 41/45.58 37/43.30 |16/43.17 13/43.50 11/42.61 16/40.59 |
|POLY-3 PERCENT (g) | 87.4% 90.4% 90.0% 85.5% |37.1% 29.9% 25.8% 39.4% |
|TERMINAL (d) | 25/26 (96%) 25/29 (86%) 24/25 (96%) 26/28 (93%) |13/30 (43%) 10/31 (32%) 8/28 (29%) 13/27 (48%) |
|FIRST INCIDENCE | 503 478 492 433 |462 622 474 525 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.235N P=0.468N P=0.352 P=0.254N |P=0.266 P=0.298N P=0.235N P=0.449 |
|POLY 3 | P=0.353N P=0.443 P=0.474 P=0.519N |P=0.322 P=0.314N P=0.184N P=0.501 |
|POLY 1.5 | P=0.315N P=0.367 P=0.509 P=0.498N |P=0.334 P=0.323N P=0.186N P=0.508 |
|POLY 6 | P=0.362N P=0.622 P=0.456 P=0.474N |P=0.319 P=0.300N P=0.182N P=0.508 |
|LOGISTIC REGRESSION| P=0.299N P=0.347 P=0.436 P=0.473N |P=0.311 P=0.297N P=0.189N P=0.501 |
|COCH-ARM / FISHERS | P=0.168N P=0.398 P=0.500 P=0.318N |P=0.411 P=0.330N P=0.184N P=0.585N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 14
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Necrosis Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.46 1/42.19 2/40.05 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 2.4% 5.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 1/25 (4%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 685 654 685 --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.216N P=0.477N P=0.652 P=0.243N |(e) (e) (e) (e) |
|POLY 3 | P=0.221N P=0.494N P=0.682 P=0.245N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.220N P=0.499N P=0.690 P=0.246N |(e) (e) (e) (e) |
|POLY 6 | P=0.220N P=0.485N P=0.670 P=0.241N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.216N P=0.499N P=0.679 P=0.243N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.209N P=0.500N P=0.691N P=0.247N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Kidney: Renal Tubule |
| Pigmentation Lipofuscin |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 1/41.96 3/41.07 0/40.04 |0/41.94 0/42.89 1/42.15 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 2.4% 7.3% 0.0% |0.0% 0.0% 2.4% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- 715 582 --- |--- --- 491 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.505N P=0.512 P=0.121 (e) |P=0.793N (e) P=0.496 (e) |
|POLY 3 | P=0.517N P=0.504 P=0.117 (e) |P=0.796N (e) P=0.501 (e) |
|POLY 1.5 | P=0.518N P=0.500 P=0.119 (e) |P=0.794N (e) P=0.500 (e) |
|POLY 6 | P=0.510N P=0.509 P=0.115 (e) |P=0.797N (e) P=0.502 (e) |
|LOGISTIC REGRESSION| P=0.489N P=0.510 P=0.111 (e) |P=0.719N (e) P=0.530 (e) |
|COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.121 (e) |P=0.785N (e) P=0.500 (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 15
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 1/40.04 |0/41.94 0/42.89 2/41.48 1/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% |0.0% 0.0% 4.8% 2.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |0/30 (0%) 0/31 (0%) 1/28 (4%) 1/27 (4%) |
|FIRST INCIDENCE | --- --- --- 727 (T) |--- --- 723 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.222 (e) (e) P=0.515 |P=0.327 (e) P=0.225 P=0.479 |
|POLY 3 | P=0.210 (e) (e) P=0.494 |P=0.321 (e) P=0.234 P=0.487 |
|POLY 1.5 | P=0.210 (e) (e) P=0.493 |P=0.326 (e) P=0.235 P=0.489 |
|POLY 6 | P=0.211 (e) (e) P=0.498 |P=0.318 (e) P=0.233 P=0.487 |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.515 |P=0.325 (e) P=0.224 P=0.479 |
|COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.354 (e) P=0.247 P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Basophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 27/50 (54%) 27/50 (54%) 22/50 (44%) 19/50 (38%) |39/50 (78%) 35/50 (70%) 40/50 (80%) 34/50 (68%) |
|POLY-3 RATE (b) | 27/42.66 27/42.45 22/41.05 19/40.36 |39/45.11 35/45.66 40/45.06 34/41.41 |
|POLY-3 PERCENT (g) | 63.3% 63.6% 53.6% 47.1% |86.5% 76.7% 88.8% 82.1% |
|TERMINAL (d) | 22/26 (85%) 25/29 (86%) 19/25 (76%) 18/28 (64%) |27/30 (90%) 27/31 (87%) 27/28 (96%) 25/27 (93%) |
|FIRST INCIDENCE | 475 577 533 640 |509 333 474 588 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.009N** P=0.325N P=0.236N P=0.019N* |P=0.506 P=0.212N P=0.340 P=0.463N |
|POLY 3 | P=0.050N P=0.581 P=0.236N P=0.093N |P=0.551N P=0.154N P=0.494 P=0.387N |
|POLY 1.5 | P=0.056N P=0.562 P=0.212N P=0.100N |P=0.475N P=0.177N P=0.487 P=0.338N |
|POLY 6 | P=0.039N* P=0.584N P=0.284N P=0.077N |P=0.581N P=0.154N P=0.491 P=0.415N |
|LOGISTIC REGRESSION| P=0.031N* P=0.467N P=0.288N P=0.053N |P=0.451N P=0.182N P=0.448 P=0.304N |
|COCH-ARM / FISHERS | P=0.045N* P=0.579N P=0.212N P=0.080N |P=0.216N P=0.247N P=0.500 P=0.184N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 16
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Clear Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 18/50 (36%) 22/50 (44%) 23/50 (46%) 16/50 (32%) |8/50 (16%) 4/50 (8%) 8/50 (16%) 6/50 (12%) |
|POLY-3 RATE (b) | 18/41.88 22/42.12 23/41.35 16/40.90 |8/42.49 4/42.89 8/42.89 6/39.51 |
|POLY-3 PERCENT (g) | 43.0% 52.2% 55.6% 39.1% |18.8% 9.3% 18.7% 15.2% |
|TERMINAL (d) | 17/26 (65%) 21/29 (72%) 19/25 (76%) 14/28 (50%) |7/30 (23%) 4/31 (13%) 3/28 (11%) 5/27 (19%) |
|FIRST INCIDENCE | 503 674 574 433 |559 728 (T) 483 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.142N P=0.403 P=0.111 P=0.309N |P=0.537 P=0.160N P=0.565 P=0.468N |
|POLY 3 | P=0.235N P=0.258 P=0.165 P=0.446N |P=0.561 P=0.170N P=0.601N P=0.443N |
|POLY 1.5 | P=0.251N P=0.250 P=0.189 P=0.460N |P=0.570N P=0.173N P=0.606N P=0.435N |
|POLY 6 | P=0.202N P=0.285 P=0.137 P=0.411N |P=0.555 P=0.166N P=0.592N P=0.446N |
|LOGISTIC REGRESSION| P=0.223N P=0.345 P=0.112 P=0.425N |P=0.573N P=0.160N P=0.601 P=0.436N |
|COCH-ARM / FISHERS | P=0.219N P=0.270 P=0.208 P=0.417N |P=0.512N P=0.178N P=0.607N P=0.387N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Eosinophilic Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 9/50 (18%) 12/50 (24%) 5/50 (10%) 4/50 (8%) |12/50 (24%) 12/50 (24%) 14/50 (28%) 10/50 (20%) |
|POLY-3 RATE (b) | 9/41.58 12/41.91 5/40.40 4/40.30 |12/43.12 12/43.83 14/42.36 10/39.64 |
|POLY-3 PERCENT (g) | 21.7% 28.6% 12.4% 9.9% |27.8% 27.4% 33.1% 25.2% |
|TERMINAL (d) | 7/26 (27%) 12/29 (41%) 3/25 (12%) 2/28 (7%) |7/30 (23%) 8/31 (26%) 10/28 (36%) 7/27 (26%) |
|FIRST INCIDENCE | 630 727 (T) 630 679 |601 510 545 672 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.033N* P=0.405 P=0.227N P=0.104N |P=0.469N P=0.557N P=0.354 P=0.503N |
|POLY 3 | P=0.038N* P=0.314 P=0.204N P=0.124N |P=0.448N P=0.577N P=0.385 P=0.492N |
|POLY 1.5 | P=0.040N* P=0.305 P=0.196N P=0.128N |P=0.424N P=0.583N P=0.394 P=0.475N |
|POLY 6 | P=0.033N* P=0.329 P=0.218N P=0.114N |P=0.469N P=0.574N P=0.371 P=0.509N |
|LOGISTIC REGRESSION| P=0.038N* P=0.370 P=0.228N P=0.115N |P=0.421N P=0.573N P=0.395 P=0.471N |
|COCH-ARM / FISHERS | P=0.037N* P=0.312 P=0.194N P=0.117N |P=0.335N P=0.592N P=0.410 P=0.405N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 17
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Hepatodiaphragmatic Nodule |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 5/50 (10%) 7/50 (14%) 9/50 (18%) |9/50 (18%) 8/50 (16%) 11/50 (22%) 14/50 (28%) |
|POLY-3 RATE (b) | 5/43.04 5/43.09 7/41.87 9/42.56 |9/44.37 8/44.23 11/44.18 14/42.88 |
|POLY-3 PERCENT (g) | 11.6% 11.6% 16.7% 21.2% |20.3% 18.1% 24.9% 32.7% |
|TERMINAL (d) | 2/26 (8%) 3/29 (10%) 3/25 (12%) 5/28 (18%) |5/30 (17%) 4/31 (13%) 5/28 (18%) 7/27 (26%) |
|FIRST INCIDENCE | 111 503 419 120 |191 589 111 273 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.131 P=0.593N P=0.359 P=0.220 |P=0.059 P=0.476N P=0.366 P=0.138 |
|POLY 3 | P=0.112 P=0.630N P=0.358 P=0.183 |P=0.066 P=0.503N P=0.396 P=0.141 |
|POLY 1.5 | P=0.111 P=0.621 P=0.368 P=0.179 |P=0.067 P=0.509N P=0.398 P=0.141 |
|POLY 6 | P=0.116 P=0.614N P=0.345 P=0.194 |P=0.065 P=0.489N P=0.392 P=0.144 |
|LOGISTIC REGRESSION| P=0.162 P=0.616N P=0.358 P=0.255 |P=0.122 P=0.511N P=0.422 P=0.210 |
|COCH-ARM / FISHERS | P=0.120 P=0.630N P=0.380 P=0.194 |P=0.086 P=0.500N P=0.402 P=0.171 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Inflammation Granulomatous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 30/50 (60%) 26/50 (52%) 32/50 (64%) 27/50 (54%) |36/50 (72%) 31/50 (62%) 37/50 (74%) 39/50 (78%) |
|POLY-3 RATE (b) | 30/45.00 26/43.47 32/42.93 27/41.94 |36/46.63 31/46.42 37/44.40 39/46.28 |
|POLY-3 PERCENT (g) | 66.7% 59.8% 74.5% 64.4% |77.2% 66.8% 83.3% 84.3% |
|TERMINAL (d) | 23/26 (89%) 22/29 (76%) 24/25 (96%) 19/28 (68%) |24/30 (80%) 23/31 (74%) 27/28 (96%) 25/27 (93%) |
|FIRST INCIDENCE | 475 478 462 604 |406 197 375 111 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.355N P=0.105N P=0.297 P=0.246N |P=0.038 * P=0.189N P=0.339 P=0.170 |
|POLY 3 | P=0.548 P=0.321N P=0.268 P=0.501N |P=0.076 P=0.176N P=0.304 P=0.261 |
|POLY 1.5 | P=0.550N P=0.316N P=0.346 P=0.484N |P=0.090 P=0.174N P=0.377 P=0.283 |
|POLY 6 | P=0.525N P=0.309N P=0.183 P=0.464N |P=0.068 P=0.183N P=0.221 P=0.248 |
|LOGISTIC REGRESSION| P=0.499N P=0.255N P=0.352 P=0.414N |P=0.073 P=0.189N P=0.469 P=0.266 |
|COCH-ARM / FISHERS | P=0.407N P=0.273N P=0.418 P=0.343N |P=0.129 P=0.198N P=0.500 P=0.322 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 18
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver |
| Mixed Cell Focus |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 8/50 (16%) 17/50 (34%) 13/50 (26%) 11/50 (22%) |19/50 (38%) 12/50 (24%) 10/50 (20%) 9/50 (18%) |
|POLY-3 RATE (b) | 8/41.85 17/41.95 13/40.07 11/40.29 |19/42.42 12/43.17 10/41.76 9/39.83 |
|POLY-3 PERCENT (g) | 19.1% 40.5% 32.4% 27.3% |44.8% 27.8% 24.0% 22.6% |
|TERMINAL (d) | 7/26 (27%) 16/29 (55%) 12/25 (48%) 10/28 (36%) |17/30 (57%) 9/31 (29%) 7/28 (25%) 7/27 (26%) |
|FIRST INCIDENCE | 519 719 679 661 |596 678 667 588 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.436N P=0.044 * P=0.120 P=0.353 |P=0.083N P=0.077N P=0.055N P=0.038N* |
|POLY 3 | P=0.530N P=0.025 * P=0.126 P=0.267 |P=0.057N P=0.074N P=0.033N* P=0.026N* |
|POLY 1.5 | P=0.532N P=0.025 * P=0.145 P=0.267 |P=0.056N P=0.083N P=0.035N* P=0.027N* |
|POLY 6 | P=0.509N P=0.026 * P=0.103 P=0.280 |P=0.056N P=0.065N P=0.031N* P=0.023N* |
|LOGISTIC REGRESSION| P=0.504N P=0.039 * P=0.105 P=0.293 |P=0.064N P=0.062N P=0.035N* P=0.028N* |
|COCH-ARM / FISHERS | P=0.477N P=0.032 * P=0.163 P=0.306 |P=0.044N* P=0.097N P=0.038N* P=0.022N* |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver: Bile Duct |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 44/50 (88%) 41/50 (82%) 32/50 (64%) 39/50 (78%) |13/50 (26%) 14/50 (28%) 11/50 (22%) 14/50 (28%) |
|POLY-3 RATE (b) | 44/47.17 41/45.36 32/43.58 39/44.71 |13/43.99 14/44.12 11/42.88 14/41.20 |
|POLY-3 PERCENT (g) | 93.3% 90.4% 73.4% 87.2% |29.6% 31.7% 25.7% 34.0% |
|TERMINAL (d) | 26/26 (100%) 27/29 (93%) 22/25 (88%) 24/28 (86%) |7/30 (23%) 8/31 (26%) 5/28 (18%) 7/27 (26%) |
|FIRST INCIDENCE | 475 478 484 433 |191 510 491 379 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.265N P=0.170N P=0.053N P=0.182N |P=0.361 P=0.533 P=0.464N P=0.403 |
|POLY 3 | P=0.274N P=0.444N P=0.004N** P=0.249N |P=0.393 P=0.504 P=0.434N P=0.418 |
|POLY 1.5 | P=0.295N P=0.403N P=0.003N** P=0.249N |P=0.402 P=0.495 P=0.431N P=0.424 |
|POLY 6 | P=0.206N P=0.447N P=0.009N** P=0.192N |P=0.391 P=0.515 P=0.436N P=0.421 |
|LOGISTIC REGRESSION| P=0.362N P=0.301N P=0.003N** P=0.265N |P=0.425 P=0.505 P=0.410N P=0.465 |
|COCH-ARM / FISHERS | P=0.217N P=0.288N P=0.005N** P=0.143N |P=0.482 P=0.500 P=0.408N P=0.500 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 19
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver: Centrilobular |
| Fatty Change |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 1/40.07 1/40.41 |1/42.39 2/43.49 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.5% 2.5% |2.4% 4.6% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- 679 622 |596 622 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.311 (e) P=0.482 P=0.510 |P=0.228N P=0.512 P=0.509N P=0.519N |
|POLY 3 | P=0.297 (e) P=0.494 P=0.496 |P=0.222N P=0.509 P=0.504N P=0.515N |
|POLY 1.5 | P=0.296 (e) P=0.498 P=0.494 |P=0.221N P=0.505 P=0.503N P=0.513N |
|POLY 6 | P=0.302 (e) P=0.489 P=0.502 |P=0.223N P=0.515 P=0.507N P=0.517N |
|LOGISTIC REGRESSION| P=0.308 (e) P=0.498 P=0.509 |P=0.198N P=0.495 P=0.491N P=0.476N |
|COCH-ARM / FISHERS | P=0.305 (e) P=0.500 P=0.500 |P=0.214N P=0.500 P=0.500N P=0.500N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Liver: Centrilobular |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 2/50 (4%) 3/50 (6%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/41.33 1/42.19 2/40.59 3/41.76 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 2.4% 2.4% 4.9% 7.2% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 699 654 561 352 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.175 P=0.742N P=0.466 P=0.291 |(e) (e) (e) (e) |
|POLY 3 | P=0.182 P=0.756N P=0.494 P=0.308 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.179 P=0.760N P=0.499 P=0.302 |(e) (e) (e) (e) |
|POLY 6 | P=0.188 P=0.750N P=0.486 P=0.319 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.222 P=0.762N P=0.499 P=0.358 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.182 P=0.753N P=0.500 P=0.309 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 20
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Congestion |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |5/50 (10%) 3/50 (6%) 1/50 (2%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 0/40.04 |5/45.26 3/45.40 1/41.86 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |11.1% 6.6% 2.4% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- --- --- |191 197 614 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.030N* P=0.356N P=0.111N P=0.042N* |
|POLY 3 | (e) (e) (e) (e) |P=0.030N* P=0.354N P=0.120N P=0.044N* |
|POLY 1.5 | (e) (e) (e) (e) |P=0.029N* P=0.355N P=0.115N P=0.041N* |
|POLY 6 | (e) (e) (e) (e) |P=0.032N* P=0.356N P=0.126N P=0.047N* |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.002N** P=0.369N P=0.062N P=0.005N** |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.024N* P=0.357N P=0.102N P=0.028N* |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 1/50 (2%) 4/50 (8%) |2/50 (4%) 1/50 (2%) 1/50 (2%) 4/50 (8%) |
|POLY-3 RATE (b) | 2/42.21 1/42.88 1/40.36 4/42.85 |2/42.06 1/43.80 1/42.04 4/42.44 |
|POLY-3 PERCENT (g) | 4.7% 2.3% 2.5% 9.3% |4.8% 2.3% 2.4% 9.4% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 111 223 587 120 |707 333 545 111 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.129 P=0.487N P=0.513N P=0.338 |P=0.114 P=0.497N P=0.524N P=0.314 |
|POLY 3 | P=0.129 P=0.494N P=0.516N P=0.344 |P=0.124 P=0.486N P=0.500N P=0.341 |
|POLY 1.5 | P=0.127 P=0.500N P=0.509N P=0.335 |P=0.125 P=0.491N P=0.501N P=0.339 |
|POLY 6 | P=0.133 P=0.485N P=0.524N P=0.357 |P=0.123 P=0.481N P=0.500N P=0.344 |
|LOGISTIC REGRESSION| P=0.314 P=0.392N P=0.627N P=0.613 |P=0.339 P=0.508N P=0.498N P=0.577 |
|COCH-ARM / FISHERS | P=0.128 P=0.500N P=0.500N P=0.339 |P=0.128 P=0.500N P=0.500N P=0.339 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 21
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung |
| Metaplasia Osseous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 0/50 (0%) |2/50 (4%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/41.22 3/41.91 0/39.89 0/40.04 |2/41.94 0/42.89 1/41.46 1/39.32 |
|POLY-3 PERCENT (g) | 0.0% 7.2% 0.0% 0.0% |4.8% 0.0% 2.4% 2.5% |
|TERMINAL (d) | 0/26 (0%) 3/29 (10%) 0/25 (0%) 0/28 (0%) |2/30 (7%) 0/31 (0%) 1/28 (4%) 1/27 (4%) |
|FIRST INCIDENCE | --- 727 (T) --- --- |728 (T) --- 728 (T) 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.261N P=0.140 (e) (e) |P=0.653N P=0.231N P=0.524N P=0.537N |
|POLY 3 | P=0.265N P=0.121 (e) (e) |P=0.633N P=0.232N P=0.504N P=0.522N |
|POLY 1.5 | P=0.269N P=0.119 (e) (e) |P=0.629N P=0.234N P=0.503N P=0.520N |
|POLY 6 | P=0.256N P=0.126 (e) (e) |P=0.636N P=0.229N P=0.505N P=0.523N |
|LOGISTIC REGRESSION| (e) P=0.140 (e) (e) |P=0.653N (e) P=0.524N P=0.537N |
|COCH-ARM / FISHERS | P=0.266N P=0.121 (e) (e) |P=0.614N P=0.247N P=0.500N P=0.500N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 6/50 (12%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 6/41.94 0/41.91 0/39.89 1/40.04 |1/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 14.3% 0.0% 0.0% 2.5% |2.4% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 5/26 (19%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |1/30 (3%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 475 --- --- 727 (T) |728 (T) --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.117N P=0.013N* P=0.019N* P=0.050N |P=0.490N P=0.493N P=0.514N P=0.521N |
|POLY 3 | P=0.114N P=0.015N* P=0.017N* P=0.062N |P=0.472N P=0.496N P=0.502N P=0.513N |
|POLY 1.5 | P=0.113N P=0.016N* P=0.016N* P=0.063N |P=0.471N P=0.498N P=0.502N P=0.511N |
|POLY 6 | P=0.115N P=0.014N* P=0.019N* P=0.059N |P=0.474N P=0.493N P=0.503N P=0.513N |
|LOGISTIC REGRESSION| P=0.123N P=0.017N* P=0.018N* P=0.062N |P=0.490N (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.118N P=0.013N* P=0.013N* P=0.056N |P=0.471N P=0.500N P=0.500N P=0.500N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 22
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 4/50 (8%) 3/50 (6%) 3/50 (6%) |3/50 (6%) 4/50 (8%) 5/50 (10%) 3/50 (6%) |
|POLY-3 RATE (b) | 3/41.85 4/41.91 3/40.52 3/40.79 |3/41.94 4/42.89 5/41.54 3/39.80 |
|POLY-3 PERCENT (g) | 7.2% 9.5% 7.4% 7.4% |7.2% 9.3% 12.0% 7.5% |
|TERMINAL (d) | 2/26 (8%) 4/29 (14%) 2/25 (8%) 2/28 (7%) |3/30 (10%) 4/31 (13%) 3/28 (11%) 1/27 (4%) |
|FIRST INCIDENCE | 519 727 (T) 521 456 |728 (T) 728 (T) 713 656 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.520N P=0.550 P=0.653 P=0.654N |P=0.578N P=0.518 P=0.321 P=0.622 |
|POLY 3 | P=0.539N P=0.501 P=0.648 P=0.651 |P=0.550N P=0.512 P=0.350 P=0.639 |
|POLY 1.5 | P=0.542N P=0.496 P=0.657 P=0.647 |P=0.546N P=0.507 P=0.351 P=0.639 |
|POLY 6 | P=0.530N P=0.511 P=0.634 P=0.661 |P=0.546N P=0.519 P=0.349 P=0.644 |
|LOGISTIC REGRESSION| P=0.535N P=0.507 P=0.663N P=0.659N |P=0.563N P=0.518 P=0.323 P=0.634 |
|COCH-ARM / FISHERS | P=0.525N P=0.500 P=0.661N P=0.661N |P=0.508N P=0.500 P=0.357 P=0.661N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolar Epithelium |
| Metaplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 2/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- --- 727 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.045 * (e) (e) P=0.254 |(e) (e) (e) (e) |
|POLY 3 | P=0.039 * (e) (e) P=0.230 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.039 * (e) (e) P=0.229 |(e) (e) (e) (e) |
|POLY 6 | P=0.039 * (e) (e) P=0.235 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.254 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 23
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolus |
| Inflammation Acute |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 1/41.65 1/42.48 0/39.89 2/41.00 |0/41.94 1/43.27 0/41.46 1/39.51 |
|POLY-3 PERCENT (g) | 2.4% 2.4% 0.0% 4.9% |0.0% 2.3% 0.0% 2.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 600 551 --- 352 |--- 622 --- 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.329 P=0.752N P=0.516N P=0.498 |P=0.444 P=0.515 (e) P=0.482 |
|POLY 3 | P=0.327 P=0.757N P=0.509N P=0.494 |P=0.444 P=0.506 (e) P=0.488 |
|POLY 1.5 | P=0.326 P=0.760N P=0.503N P=0.491 |P=0.446 P=0.503 (e) P=0.489 |
|POLY 6 | P=0.330 P=0.751N P=0.516N P=0.501 |P=0.445 P=0.510 (e) P=0.489 |
|LOGISTIC REGRESSION| P=0.395 P=0.755N P=0.514N P=0.556 |P=0.466 P=0.497 (e) P=0.493 |
|COCH-ARM / FISHERS | P=0.332 P=0.753N P=0.500N P=0.500 |P=0.459 P=0.500 (e) P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lung: Alveolus |
| Inflammation Chronic Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 6/50 (12%) 11/50 (22%) 14/50 (28%) |2/50 (4%) 25/50 (50%) 27/50 (54%) 34/50 (68%) |
|POLY-3 RATE (b) | 0/41.22 6/41.97 11/41.70 14/41.63 |2/41.94 25/45.19 27/43.59 34/42.81 |
|POLY-3 PERCENT (g) | 0.0% 14.3% 26.4% 33.6% |4.8% 55.3% 61.9% 79.4% |
|TERMINAL (d) | 0/26 (0%) 5/29 (17%) 6/25 (24%) 9/28 (32%) |2/30 (7%) 17/31 (55%) 21/28 (75%) 23/27 (85%) |
|FIRST INCIDENCE | --- 713 484 433 |728 (T) 510 483 495 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P<0.001 ** P=0.024 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.016 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.015 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.017 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.020 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.013 * P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 24
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mediastinal |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 3/50 (6%) 1/50 (2%) |
|POLY-3 RATE (b) | 0/41.22 2/41.91 2/39.89 1/40.04 |0/41.94 2/42.89 3/41.46 1/39.32 |
|POLY-3 PERCENT (g) | 0.0% 4.8% 5.0% 2.5% |0.0% 4.7% 7.2% 2.5% |
|TERMINAL (d) | 0/26 (0%) 2/29 (7%) 2/25 (8%) 1/28 (4%) |0/30 (0%) 2/31 (7%) 3/28 (11%) 1/27 (4%) |
|FIRST INCIDENCE | --- 727 (T) 727 (T) 727 (T) |--- 728 (T) 728 (T) 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.626 P=0.262 P=0.229 P=0.515 |P=0.573 P=0.245 P=0.108 P=0.479 |
|POLY 3 | P=0.599 P=0.241 P=0.229 P=0.494 |P=0.577 P=0.242 P=0.116 P=0.487 |
|POLY 1.5 | P=0.597 P=0.237 P=0.234 P=0.493 |P=0.582 P=0.240 P=0.117 P=0.489 |
|POLY 6 | P=0.608 P=0.246 P=0.222 P=0.498 |P=0.575 P=0.245 P=0.115 P=0.487 |
|LOGISTIC REGRESSION| (e) P=0.262 P=0.229 P=0.515 |(e) P=0.245 P=0.108 P=0.479 |
|COCH-ARM / FISHERS | P=0.615 P=0.247 P=0.247 P=0.500 |P=0.617 P=0.247 P=0.121 P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mediastinal |
| Hemorrhage |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 3/50 (6%) 2/50 (4%) 3/50 (6%) |
|POLY-3 RATE (b) | 2/41.71 0/41.91 0/39.89 1/41.00 |0/41.94 3/42.94 2/42.06 3/40.18 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 2.4% |0.0% 7.0% 4.8% 7.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 2/31 (7%) 0/28 (0%) 1/27 (4%) |
|FIRST INCIDENCE | 589 --- --- 237 |--- 716 545 525 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.648N P=0.240N P=0.272N P=0.508N |P=0.202 P=0.128 P=0.230 P=0.111 |
|POLY 3 | P=0.648N P=0.236N P=0.247N P=0.506N |P=0.215 P=0.123 P=0.237 P=0.111 |
|POLY 1.5 | P=0.647N P=0.238N P=0.241N P=0.508N |P=0.215 P=0.121 P=0.237 P=0.111 |
|POLY 6 | P=0.649N P=0.232N P=0.256N P=0.501N |P=0.218 P=0.125 P=0.238 P=0.112 |
|LOGISTIC REGRESSION| P=0.569N P=0.237N P=0.237N P=0.420N |P=0.229 P=0.127 P=0.241 P=0.123 |
|COCH-ARM / FISHERS | P=0.646N P=0.247N P=0.247N P=0.500N |P=0.235 P=0.121 P=0.247 P=0.121 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 25
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mediastinal |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 7/50 (14%) 2/50 (4%) 1/50 (2%) |2/50 (4%) 3/50 (6%) 3/50 (6%) 6/50 (12%) |
|POLY-3 RATE (b) | 2/41.22 7/42.91 2/39.89 1/40.04 |2/41.95 3/42.94 3/41.48 6/39.55 |
|POLY-3 PERCENT (g) | 4.9% 16.3% 5.0% 2.5% |4.8% 7.0% 7.2% 15.2% |
|TERMINAL (d) | 2/26 (8%) 6/29 (21%) 2/25 (8%) 1/28 (4%) |1/30 (3%) 2/31 (7%) 2/28 (7%) 5/27 (19%) |
|FIRST INCIDENCE | 727 (T) 131 727 (T) 727 (T) |726 716 723 667 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.107N P=0.104 P=0.683 P=0.474N |P=0.058 P=0.512 P=0.466 P=0.107 |
|POLY 3 | P=0.119N P=0.087 P=0.683 P=0.510N |P=0.066 P=0.511 P=0.495 P=0.113 |
|POLY 1.5 | P=0.122N P=0.083 P=0.690 P=0.513N |P=0.068 P=0.506 P=0.496 P=0.115 |
|POLY 6 | P=0.112N P=0.093 P=0.672 P=0.503N |P=0.065 P=0.517 P=0.493 P=0.113 |
|LOGISTIC REGRESSION| P=0.121N P=0.081 P=0.683 P=0.474N |P=0.057 P=0.519 P=0.468 P=0.110 |
|COCH-ARM / FISHERS | P=0.116N P=0.080 P=0.691N P=0.500N |P=0.082 P=0.500 P=0.500 P=0.134 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mediastinal |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 4/50 (8%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 1/39.89 0/40.04 |1/41.94 0/42.89 4/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 2.5% 0.0% |2.4% 0.0% 9.7% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 1/25 (4%) 0/28 (0%) |1/30 (3%) 0/31 (0%) 4/28 (14%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- 727 (T) --- |728 (T) --- 728 (T) --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.778N (e) P=0.492 (e) |P=0.477N P=0.493N P=0.157 P=0.521N |
|POLY 3 | P=0.790N (e) P=0.493 (e) |P=0.477N P=0.496N P=0.174 P=0.513N |
|POLY 1.5 | P=0.790N (e) P=0.498 (e) |P=0.470N P=0.498N P=0.175 P=0.511N |
|POLY 6 | P=0.789N (e) P=0.487 (e) |P=0.481N P=0.493N P=0.172 P=0.513N |
|LOGISTIC REGRESSION| (e) (e) P=0.492 (e) |P=0.477N (e) P=0.157 (e) |
|COCH-ARM / FISHERS | P=0.785N (e) P=0.500 (e) |P=0.436N P=0.500N P=0.181 P=0.500N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 26
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Ectasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 2/50 (4%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 1/49 (2%) |
|POLY-3 RATE (b) | 0/41.22 2/42.19 2/39.89 0/39.18 |0/41.94 0/42.89 0/41.46 1/38.51 |
|POLY-3 PERCENT (g) | 0.0% 4.7% 5.0% 0.0% |0.0% 0.0% 0.0% 2.6% |
|TERMINAL (d) | 0/26 (0%) 1/29 (3%) 2/25 (8%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/26 (0%) |
|FIRST INCIDENCE | --- 654 727 (T) --- |--- --- --- 680 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.378N P=0.261 P=0.229 (e) |P=0.200 (e) (e) P=0.482 |
|POLY 3 | P=0.404N P=0.242 P=0.229 (e) |P=0.201 (e) (e) P=0.483 |
|POLY 1.5 | P=0.407N P=0.238 P=0.234 (e) |P=0.202 (e) (e) P=0.484 |
|POLY 6 | P=0.396N P=0.249 P=0.222 (e) |P=0.200 (e) (e) P=0.483 |
|LOGISTIC REGRESSION| P=0.400N P=0.239 P=0.229 (e) |P=0.205 (e) (e) P=0.488 |
|COCH-ARM / FISHERS | P=0.392N P=0.247 P=0.247 (e) |P=0.211 (e) (e) P=0.495 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Hyperplasia Lymphoid |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 1/49 (2%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 2/49 (4%) |
|POLY-3 RATE (b) | 0/41.22 1/42.41 1/40.59 1/40.07 |0/41.94 0/42.89 2/41.75 2/39.50 |
|POLY-3 PERCENT (g) | 0.0% 2.4% 2.5% 2.5% |0.0% 0.0% 4.8% 5.1% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/26 (0%) |
|FIRST INCIDENCE | --- 577 484 352 |--- --- 667 139 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.472 P=0.505 P=0.500 P=0.487 |P=0.109 (e) P=0.236 P=0.228 |
|POLY 3 | P=0.472 P=0.506 P=0.497 P=0.494 |P=0.107 (e) P=0.236 P=0.224 |
|POLY 1.5 | P=0.468 P=0.502 P=0.500 P=0.492 |P=0.109 (e) P=0.236 P=0.224 |
|POLY 6 | P=0.480 P=0.512 P=0.492 P=0.500 |P=0.106 (e) P=0.236 P=0.224 |
|LOGISTIC REGRESSION| P=0.582 P=0.509 P=0.417 P=0.604 |P=0.179 (e) P=0.236 P=0.358 |
|COCH-ARM / FISHERS | P=0.478 P=0.500 P=0.500 P=0.495 |P=0.119 (e) P=0.247 P=0.242 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 27
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Infiltration Cellular Histiocyte |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 1/50 (2%) 18/50 (36%) 39/49 (80%) |0/50 (0%) 3/50 (6%) 27/50 (54%) 41/49 (84%) |
|POLY-3 RATE (b) | 1/41.24 1/41.91 18/42.35 39/46.11 |0/41.94 3/43.87 27/43.55 41/43.68 |
|POLY-3 PERCENT (g) | 2.4% 2.4% 42.5% 84.6% |0.0% 6.8% 62.0% 93.9% |
|TERMINAL (d) | 0/26 (0%) 1/29 (3%) 10/25 (40%) 24/28 (86%) |0/30 (0%) 2/31 (7%) 21/28 (75%) 26/26 (100%) |
|FIRST INCIDENCE | 721 727 (T) 492 237 |--- 197 405 111 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P<0.001 ** P=0.748N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.128 P<0.001 ** P<0.001 ** |
|POLY 3 | P<0.001 ** P=0.757N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.127 P<0.001 ** P<0.001 ** |
|POLY 1.5 | P<0.001 ** P=0.760N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.124 P<0.001 ** P<0.001 ** |
|POLY 6 | P<0.001 ** P=0.752N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.129 P<0.001 ** P<0.001 ** |
|LOGISTIC REGRESSION| P<0.001 ** P=0.747N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.110 P<0.001 ** P<0.001 ** |
|COCH-ARM / FISHERS | P<0.001 ** P=0.753N P<0.001 ** P<0.001 ** |P<0.001 ** P=0.121 P<0.001 ** P<0.001 ** |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Lymph Node, Mesenteric |
| Inflammation Granulomatous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 3/49 (6%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 3/39.61 |0/41.94 0/42.89 0/41.46 0/38.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 7.6% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/26 (0%) |
|FIRST INCIDENCE | --- --- --- 604 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.011 * (e) (e) P=0.136 |(e) (e) (e) (e) |
|POLY 3 | P=0.007 ** (e) (e) P=0.111 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.007 ** (e) (e) P=0.109 |(e) (e) (e) (e) |
|POLY 6 | P=0.007 ** (e) (e) P=0.116 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.008 ** (e) (e) P=0.112 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.008 ** (e) (e) P=0.117 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 28
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 25/49 (51%) 37/49 (76%) 31/50 (62%) 17/48 (35%) |2/50 (4%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 25/45.36 37/47.83 31/46.70 17/43.03 |2/42.42 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 55.1% 77.4% 66.4% 39.5% |4.7% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 12/26 (46%) 19/28 (68%) 15/25 (60%) 8/28 (29%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 475 131 419 237 |596 --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.012N* P=0.083 P=0.161 P=0.102N |P=0.252N P=0.248N P=0.256N P=0.261N |
|POLY 3 | P=0.003N** P=0.016 * P=0.180 P=0.101N |P=0.240N P=0.234N P=0.242N P=0.254N |
|POLY 1.5 | P=0.003N** P=0.012 * P=0.182 P=0.105N |P=0.239N P=0.236N P=0.241N P=0.251N |
|POLY 6 | P=0.003N** P=0.023 * P=0.176 P=0.096N |P=0.241N P=0.233N P=0.244N P=0.256N |
|LOGISTIC REGRESSION| P=0.002N** P=0.012 * P=0.198 P=0.083N |P=0.235N P=0.239N P=0.236N P=0.237N |
|COCH-ARM / FISHERS | P=0.002N** P=0.010 * P=0.184 P=0.089N |P=0.238N P=0.247N P=0.247N P=0.247N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Mammary Gland |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/49 (0%) 0/49 (0%) 0/50 (0%) 0/48 (0%) |6/50 (12%) 3/50 (6%) 3/50 (6%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/41.21 0/40.91 0/39.89 0/39.24 |6/43.58 3/42.95 3/42.62 2/40.15 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |13.8% 7.0% 7.0% 5.0% |
|TERMINAL (d) | 0/26 (0%) 0/28 (0%) 0/25 (0%) 0/28 (0%) |3/30 (10%) 2/31 (7%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- --- --- |462 714 483 518 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | (e) (e) (e) (e) |P=0.203N P=0.236N P=0.264N P=0.171N |
|POLY 3 | (e) (e) (e) (e) |P=0.184N P=0.248N P=0.252N P=0.160N |
|POLY 1.5 | (e) (e) (e) (e) |P=0.181N P=0.246N P=0.250N P=0.155N |
|POLY 6 | (e) (e) (e) (e) |P=0.185N P=0.250N P=0.255N P=0.162N |
|LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.143N P=0.244N P=0.231N P=0.117N |
|COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.161N P=0.243N P=0.243N P=0.134N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 29
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Mammary Gland: Duct |
| Dilatation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 12/49 (24%) 24/49 (49%) 27/50 (54%) 15/48 (31%) |29/50 (58%) 15/50 (30%) 20/50 (40%) 23/50 (46%) |
|POLY-3 RATE (b) | 12/43.36 24/42.70 27/42.98 15/40.74 |29/45.21 15/43.74 20/45.16 23/42.79 |
|POLY-3 PERCENT (g) | 27.7% 56.2% 62.8% 36.8% |64.2% 34.3% 44.3% 53.8% |
|TERMINAL (d) | 4/26 (15%) 15/28 (54%) 17/25 (68%) 10/28 (36%) |19/30 (63%) 11/31 (36%) 9/28 (32%) 14/27 (52%) |
|FIRST INCIDENCE | 505 478 462 433 |462 589 483 495 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.329N P=0.035 * P=0.003 ** P=0.367 |P=0.378 P=0.006N** P=0.126N P=0.321N |
|POLY 3 | P=0.435N P=0.005 ** P<0.001 ** P=0.252 |P=0.490 P=0.003N** P=0.042N* P=0.215N |
|POLY 1.5 | P=0.446N P=0.005 ** P<0.001 ** P=0.249 |P=0.482 P=0.003N** P=0.046N* P=0.216N |
|POLY 6 | P=0.409N P=0.006 ** P<0.001 ** P=0.266 |P=0.515 P=0.003N** P=0.036N* P=0.203N |
|LOGISTIC REGRESSION| P=0.411N P=0.008 ** P<0.001 ** P=0.272 |P=0.461 P=0.003N** P=0.057N P=0.222N |
|COCH-ARM / FISHERS | P=0.366N P=0.010 * P=0.002 ** P=0.303 |P=0.537N P=0.004N** P=0.055N P=0.158N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Mesentery: Fat |
| Inflammation Granulomatous |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/9 (0%) 0/11 (0%) 0/9 (0%) 2/13 (15%) |0/8 (0%) 0/4 (0%) 0/6 (0%) 0/9 (0%) |
|POLY-3 RATE (b) | 0/7.11 0/10.79 0/6.86 2/10.93 |0/6.66 0/3.28 0/3.89 0/6.50 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 18.3% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/4 (0%) 0/7 (0%) 0/3 (0%) 2/7 (29%) |0/6 (0%) 0/3 (0%) 0/1 (0%) 0/3 (0%) |
|FIRST INCIDENCE | --- --- --- 727 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.077 (e) (e) P=0.362 |(e) (e) (e) (e) |
|POLY 3 | P=0.059 (e) (e) P=0.331 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.062 (e) (e) P=0.326 |(e) (e) (e) (e) |
|POLY 6 | P=0.055 (e) (e) P=0.335 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.362 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.068 (e) (e) P=0.338 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 30
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Mesentery: Fat |
| Necrosis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 7/9 (78%) 10/11 (91%) 9/9 (100%) 8/13 (62%) |7/8 (88%) 4/4 (100%) 6/6 (100%) 9/9 (100%) |
|POLY-3 RATE (b) | 7/8.86 10/11.00 9/9.00 8/12.63 |7/7.45 4/4.00 6/6.00 9/9.00 |
|POLY-3 PERCENT (g) | 79.0% 90.9% 100.0% 63.4% |93.9% 100.0% 100.0% 100.0% |
|TERMINAL (d) | 4/4 (100%) 6/7 (86%) 3/3 (100%) 3/7 (43%) |6/6 (100%) 3/3 (100%) 1/1 (100%) 3/3 (100%) |
|FIRST INCIDENCE | 503 705 484 484 |427 474 483 273 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.363N P=0.634 P=0.226 P=0.515N |P=0.018 * P=0.753N P=0.105 P=0.056 |
|POLY 3 | P=0.081N P=0.457 P=0.240 P=0.384N |P=0.775 P=0.932 P=0.897 P=0.861 |
|POLY 1.5 | P=0.076N P=0.442 P=0.232 P=0.379N |P=0.573 P=0.790 P=0.724 P=0.656 |
|POLY 6 | P=0.087N P=0.486 P=0.257 P=0.387N |P=0.998 P=1.000 P=1.000 P=1.000 |
|LOGISTIC REGRESSION| P=0.060N P=0.309 P=0.250 P=0.412N |P=0.353 P=0.643 P=0.512 P=0.421 |
|COCH-ARM / FISHERS | P=0.076N P=0.421 P=0.235 P=0.372N |P=0.414 P=0.667 P=0.571 P=0.471 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Nose |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 9/50 (18%) 7/50 (14%) 8/50 (16%) 9/50 (18%) |6/50 (12%) 3/50 (6%) 7/50 (14%) 5/50 (10%) |
|POLY-3 RATE (b) | 9/42.45 7/43.28 8/40.77 9/40.97 |6/42.30 3/43.17 7/42.48 5/39.33 |
|POLY-3 PERCENT (g) | 21.2% 16.2% 19.6% 22.0% |14.2% 7.0% 16.5% 12.7% |
|TERMINAL (d) | 4/26 (15%) 1/29 (3%) 4/25 (16%) 7/28 (25%) |5/30 (17%) 2/31 (7%) 5/28 (18%) 4/27 (15%) |
|FIRST INCIDENCE | 547 577 586 433 |629 653 111 727 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.465 P=0.343N P=0.561N P=0.571N |P=0.481 P=0.223N P=0.458 P=0.566N |
|POLY 3 | P=0.417 P=0.375N P=0.537N P=0.572 |P=0.488 P=0.231N P=0.503 P=0.551N |
|POLY 1.5 | P=0.422 P=0.390N P=0.515N P=0.569 |P=0.501 P=0.236N P=0.506 P=0.543N |
|POLY 6 | P=0.412 P=0.348N P=0.567N P=0.583 |P=0.476 P=0.224N P=0.497 P=0.557N |
|LOGISTIC REGRESSION| P=0.433 P=0.392N P=0.523N P=0.578 |P=0.520 P=0.228N P=0.499 P=0.549N |
|COCH-ARM / FISHERS | P=0.462 P=0.393N P=0.500N P=0.602N |P=0.559 P=0.243N P=0.500 P=0.500N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 31
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Nose |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.33 1/41.97 0/39.89 0/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 2.4% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 699 713 --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.180N P=0.463N P=0.266N P=0.235N |(e) (e) (e) (e) |
|POLY 3 | P=0.172N P=0.495N P=0.245N P=0.244N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.171N P=0.500N P=0.240N P=0.245N |(e) (e) (e) (e) |
|POLY 6 | P=0.172N P=0.486N P=0.252N P=0.240N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.174N P=0.485N P=0.254N P=0.239N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.169N P=0.500N P=0.247N P=0.247N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Ovary |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |4/50 (8%) 5/50 (10%) 7/50 (14%) 5/50 (10%) |
|POLY-3 RATE (b) | |4/43.47 5/43.27 7/42.34 5/40.50 |
|POLY-3 PERCENT (g) | |9.2% 11.6% 16.5% 12.3% |
|TERMINAL (d) | |2/30 (7%) 4/31 (13%) 5/28 (18%) 3/27 (11%) |
|FIRST INCIDENCE | |191 622 405 111 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.429 P=0.517 P=0.233 P=0.449 |
|POLY 3 | |P=0.445 P=0.497 P=0.244 P=0.456 |
|POLY 1.5 | |P=0.457 P=0.494 P=0.248 P=0.463 |
|POLY 6 | |P=0.438 P=0.503 P=0.239 P=0.453 |
|LOGISTIC REGRESSION| |P=0.547 P=0.491 P=0.270 P=0.600 |
|COCH-ARM / FISHERS | |P=0.507 P=0.500 P=0.262 P=0.500 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 32
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 12/50 (24%) 14/50 (28%) 14/50 (28%) 16/50 (32%) |7/50 (14%) 12/50 (24%) 11/50 (22%) 8/50 (16%) |
|POLY-3 RATE (b) | 12/42.89 14/43.56 14/40.87 16/41.13 |7/42.68 12/43.77 11/44.11 8/41.24 |
|POLY-3 PERCENT (g) | 28.0% 32.1% 34.3% 38.9% |16.4% 27.4% 24.9% 19.4% |
|TERMINAL (d) | 7/26 (27%) 9/29 (31%) 12/25 (48%) 11/28 (39%) |6/30 (20%) 10/31 (32%) 5/28 (18%) 5/27 (19%) |
|FIRST INCIDENCE | 503 551 574 622 |462 539 375 379 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.277 P=0.511 P=0.354 P=0.303 |P=0.542N P=0.171 P=0.193 P=0.424 |
|POLY 3 | P=0.187 P=0.425 P=0.349 P=0.201 |P=0.477N P=0.163 P=0.236 P=0.471 |
|POLY 1.5 | P=0.194 P=0.407 P=0.383 P=0.201 |P=0.478N P=0.157 P=0.229 P=0.467 |
|POLY 6 | P=0.193 P=0.464 P=0.304 P=0.217 |P=0.470N P=0.172 P=0.243 P=0.481 |
|LOGISTIC REGRESSION| P=0.208 P=0.413 P=0.371 P=0.220 |P=0.442N P=0.162 P=0.221 P=0.487 |
|COCH-ARM / FISHERS | P=0.249 P=0.410 P=0.410 P=0.252 |P=0.428N P=0.154 P=0.218 P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pancreas: Acinus |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 2/41.91 1/39.89 0/40.04 |1/41.94 1/42.93 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 4.8% 2.5% 0.0% |2.4% 2.3% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 2/29 (7%) 1/25 (4%) 0/28 (0%) |1/30 (3%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- 727 (T) 727 (T) --- |728 (T) 719 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.378N P=0.262 P=0.492 (e) |P=0.325N P=0.760N P=0.514N P=0.521N |
|POLY 3 | P=0.392N P=0.241 P=0.493 (e) |P=0.311N P=0.756N P=0.502N P=0.513N |
|POLY 1.5 | P=0.395N P=0.237 P=0.498 (e) |P=0.311N P=0.758N P=0.502N P=0.511N |
|POLY 6 | P=0.384N P=0.246 P=0.487 (e) |P=0.312N P=0.753N P=0.503N P=0.513N |
|LOGISTIC REGRESSION| (e) P=0.262 P=0.492 (e) |P=0.322N P=0.754N (e) (e) |
|COCH-ARM / FISHERS | P=0.385N P=0.247 P=0.500 (e) |P=0.305N P=0.753N P=0.500N P=0.500N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 33
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Angiectasis |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |1/50 (2%) 2/50 (4%) 2/50 (4%) 2/50 (4%) |
|POLY-3 RATE (b) | 0/41.22 1/41.91 0/39.89 1/40.04 |1/41.94 2/43.32 2/41.46 2/39.69 |
|POLY-3 PERCENT (g) | 0.0% 2.4% 0.0% 2.5% |2.4% 4.6% 4.8% 5.0% |
|TERMINAL (d) | 0/26 (0%) 1/29 (3%) 0/25 (0%) 1/28 (4%) |1/30 (3%) 0/31 (0%) 2/28 (7%) 1/27 (4%) |
|FIRST INCIDENCE | --- 727 (T) --- 727 (T) |728 (T) 622 728 (T) 624 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.467 P=0.522 (e) P=0.515 |P=0.450 P=0.519 P=0.476 P=0.476 |
|POLY 3 | P=0.452 P=0.503 (e) P=0.494 |P=0.456 P=0.511 P=0.496 P=0.481 |
|POLY 1.5 | P=0.450 P=0.500 (e) P=0.493 |P=0.460 P=0.506 P=0.497 P=0.482 |
|POLY 6 | P=0.458 P=0.509 (e) P=0.498 |P=0.456 P=0.518 P=0.495 P=0.483 |
|LOGISTIC REGRESSION| (e) P=0.522 (e) P=0.515 |P=0.463 P=0.503 P=0.476 P=0.482 |
|COCH-ARM / FISHERS | P=0.459 P=0.500 (e) P=0.500 |P=0.489 P=0.500 P=0.500 P=0.500 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 3/50 (6%) 5/50 (10%) 2/50 (4%) |20/50 (40%) 21/50 (42%) 18/50 (36%) 22/50 (44%) |
|POLY-3 RATE (b) | 3/41.58 3/41.91 5/40.86 2/40.47 |20/44.24 21/44.37 18/43.58 22/42.21 |
|POLY-3 PERCENT (g) | 7.2% 7.2% 12.2% 4.9% |45.2% 47.3% 41.3% 52.1% |
|TERMINAL (d) | 1/26 (4%) 3/29 (10%) 3/25 (12%) 1/28 (4%) |13/30 (43%) 15/31 (48%) 12/28 (43%) 14/27 (52%) |
|FIRST INCIDENCE | 630 727 (T) 526 604 |427 474 483 495 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.389N P=0.621N P=0.334 P=0.483N |P=0.238 P=0.547 P=0.500N P=0.301 |
|POLY 3 | P=0.414N P=0.659N P=0.346 P=0.512N |P=0.297 P=0.505 P=0.438N P=0.333 |
|POLY 1.5 | P=0.417N P=0.661 P=0.354 P=0.516N |P=0.299 P=0.502 P=0.434N P=0.333 |
|POLY 6 | P=0.405N P=0.651N P=0.332 P=0.503N |P=0.313 P=0.509 P=0.448N P=0.350 |
|LOGISTIC REGRESSION| P=0.411N P=0.648N P=0.352 P=0.511N |P=0.283 P=0.526 P=0.430N P=0.333 |
|COCH-ARM / FISHERS | P=0.395N P=0.661N P=0.357 P=0.500N |P=0.390 P=0.500 P=0.418N P=0.420 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 34
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 2/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- --- 727 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.045 * (e) (e) P=0.254 |(e) (e) (e) (e) |
|POLY 3 | P=0.039 * (e) (e) P=0.230 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.039 * (e) (e) P=0.229 |(e) (e) (e) (e) |
|POLY 6 | P=0.039 * (e) (e) P=0.235 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.254 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.042 * (e) (e) P=0.247 |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Pituitary Gland: Pars Distalis |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 11/50 (22%) 12/50 (24%) 17/50 (34%) 9/50 (18%) |16/50 (32%) 15/50 (30%) 10/50 (20%) 13/50 (26%) |
|POLY-3 RATE (b) | 11/42.30 12/42.77 17/42.98 9/42.73 |16/43.43 15/44.54 10/42.69 13/40.86 |
|POLY-3 PERCENT (g) | 26.0% 28.1% 39.6% 21.1% |36.9% 33.7% 23.4% 31.8% |
|TERMINAL (d) | 6/26 (23%) 9/29 (31%) 10/25 (40%) 5/28 (18%) |14/30 (47%) 11/31 (36%) 7/28 (25%) 8/27 (30%) |
|FIRST INCIDENCE | 519 577 419 261 |406 474 491 518 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.285N P=0.585N P=0.117 P=0.387N |P=0.452N P=0.457N P=0.161N P=0.441N |
|POLY 3 | P=0.267N P=0.512 P=0.131 P=0.389N |P=0.395N P=0.465N P=0.128N P=0.398N |
|POLY 1.5 | P=0.285N P=0.498 P=0.136 P=0.407N |P=0.387N P=0.483N P=0.130N P=0.397N |
|POLY 6 | P=0.245N P=0.538 P=0.124 P=0.365N |P=0.387N P=0.437N P=0.122N P=0.379N |
|LOGISTIC REGRESSION| P=0.300N P=0.520 P=0.125 P=0.403N |P=0.385N P=0.485N P=0.131N P=0.393N |
|COCH-ARM / FISHERS | P=0.282N P=0.500 P=0.133 P=0.402N |P=0.316N P=0.500N P=0.127N P=0.330N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 35
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 2/50 (4%) | |
|POLY-3 RATE (b) | 0/41.22 0/41.91 3/40.43 2/40.04 | |
|POLY-3 PERCENT (g) | 0.0% 0.0% 7.4% 5.0% | |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 2/25 (8%) 2/28 (7%) | |
|FIRST INCIDENCE | --- --- 561 727 (T) | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.165 (e) P=0.119 P=0.254 | |
|POLY 3 | P=0.143 (e) P=0.114 P=0.230 | |
|POLY 1.5 | P=0.143 (e) P=0.118 P=0.229 | |
|POLY 6 | P=0.145 (e) P=0.110 P=0.235 | |
|LOGISTIC REGRESSION| P=0.150 (e) P=0.120 P=0.254 | |
|COCH-ARM / FISHERS | P=0.157 (e) P=0.121 P=0.247 | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 0/50 (0%) 0/50 (0%) | |
|POLY-3 RATE (b) | 1/41.22 2/41.91 0/39.89 0/40.04 | |
|POLY-3 PERCENT (g) | 2.4% 4.8% 0.0% 0.0% | |
|TERMINAL (d) | 1/26 (4%) 2/29 (7%) 0/25 (0%) 0/28 (0%) | |
|FIRST INCIDENCE | 727 (T) 727 (T) --- --- | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.210N P=0.538 P=0.508N P=0.485N | |
|POLY 3 | P=0.216N P=0.506 P=0.507N P=0.506N | |
|POLY 1.5 | P=0.218N P=0.500 P=0.502N P=0.507N | |
|POLY 6 | P=0.213N P=0.515 P=0.513N P=0.502N | |
|LOGISTIC REGRESSION| P=0.210N P=0.538 (e) (e) | |
|COCH-ARM / FISHERS | P=0.214N P=0.500 P=0.500N P=0.500N | |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 36
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Inflammation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 1/50 (2%) | |
|POLY-3 RATE (b) | 1/41.85 0/41.91 2/39.89 1/40.04 | |
|POLY-3 PERCENT (g) | 2.4% 0.0% 5.0% 2.5% | |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 2/25 (8%) 1/28 (4%) | |
|FIRST INCIDENCE | 519 --- 727 (T) 727 (T) | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.558 P=0.504N P=0.491 P=0.759 | |
|POLY 3 | P=0.537 P=0.500N P=0.483 P=0.751 | |
|POLY 1.5 | P=0.539 P=0.502N P=0.493 P=0.751 | |
|POLY 6 | P=0.538 P=0.496N P=0.470 P=0.754 | |
|LOGISTIC REGRESSION| P=0.552 P=0.483N P=0.500 P=0.755N | |
|COCH-ARM / FISHERS | P=0.558 P=0.500N P=0.500 P=0.753N | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Preputial Gland |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 35/50 (70%) 44/50 (88%) 42/50 (84%) 37/50 (74%) | |
|POLY-3 RATE (b) | 35/45.89 44/47.42 42/48.28 37/45.20 | |
|POLY-3 PERCENT (g) | 76.3% 92.8% 87.0% 81.9% | |
|TERMINAL (d) | 20/26 (77%) 26/29 (90%) 21/25 (84%) 24/28 (86%) | |
|FIRST INCIDENCE | 503 223 462 161 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.393N P=0.230 P=0.115 P=0.521 | |
|POLY 3 | P=0.477N P=0.019 * P=0.128 P=0.339 | |
|POLY 1.5 | P=0.466N P=0.016 * P=0.109 P=0.332 | |
|POLY 6 | P=0.472N P=0.033 * P=0.161 P=0.369 | |
|LOGISTIC REGRESSION| P=0.477N P=0.016 * P=0.073 P=0.307 | |
|COCH-ARM / FISHERS | P=0.355N P=0.024 * P=0.077 P=0.412 | |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 37
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Prostate |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 18/50 (36%) 16/50 (32%) 19/50 (38%) 18/49 (37%) | |
|POLY-3 RATE (b) | 18/43.92 16/44.15 19/43.66 18/42.17 | |
|POLY-3 PERCENT (g) | 41.0% 36.2% 43.5% 42.7% | |
|TERMINAL (d) | 10/26 (39%) 7/29 (24%) 8/25 (32%) 10/28 (36%) | |
|FIRST INCIDENCE | 503 478 462 352 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.473 P=0.335N P=0.419 P=0.534N | |
|POLY 3 | P=0.401 P=0.406N P=0.490 P=0.523 | |
|POLY 1.5 | P=0.394 P=0.421N P=0.504 P=0.509 | |
|POLY 6 | P=0.425 P=0.379N P=0.474 P=0.557 | |
|LOGISTIC REGRESSION| P=0.410 P=0.415N P=0.495 P=0.520 | |
|COCH-ARM / FISHERS | P=0.444 P=0.417N P=0.500 P=0.553 | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Salivary Glands: Parotid Gland |
| Atrophy Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/49 (2%) 0/50 (0%) |2/50 (4%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/41.22 0/41.91 1/39.56 0/40.04 |2/41.94 1/42.93 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 2.4% 0.0% 2.5% 0.0% |4.8% 2.3% 0.0% 0.0% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |2/30 (7%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 727 (T) --- 561 --- |728 (T) 719 --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.457N P=0.478N P=0.759 P=0.485N |P=0.186N P=0.496N P=0.253N P=0.261N |
|POLY 3 | P=0.468N P=0.497N P=0.752 P=0.506N |P=0.175N P=0.492N P=0.239N P=0.251N |
|POLY 1.5 | P=0.467N P=0.500N P=0.755 P=0.507N |P=0.174N P=0.496N P=0.239N P=0.250N |
|POLY 6 | P=0.469N P=0.491N P=0.747 P=0.502N |P=0.176N P=0.487N P=0.240N P=0.252N |
|LOGISTIC REGRESSION| P=0.454N (e) P=0.758 (e) |P=0.183N P=0.485N (e) (e) |
|COCH-ARM / FISHERS | P=0.459N P=0.500N P=0.747 P=0.500N |P=0.169N P=0.500N P=0.247N P=0.247N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 38
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Seminal Vesicle |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 4/50 (8%) 0/50 (0%) 2/50 (4%) 2/49 (4%) | |
|POLY-3 RATE (b) | 4/42.05 0/41.91 2/41.32 2/40.18 | |
|POLY-3 PERCENT (g) | 9.5% 0.0% 4.8% 5.0% | |
|TERMINAL (d) | 2/26 (8%) 0/29 (0%) 0/25 (0%) 1/28 (4%) | |
|FIRST INCIDENCE | 503 --- 462 120 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.556N P=0.059N P=0.361N P=0.334N | |
|POLY 3 | P=0.559N P=0.060N P=0.344N P=0.358N | |
|POLY 1.5 | P=0.558N P=0.061N P=0.338N P=0.359N | |
|POLY 6 | P=0.559N P=0.058N P=0.357N P=0.351N | |
|LOGISTIC REGRESSION| P=0.459N P=0.063N P=0.358N P=0.292N | |
|COCH-ARM / FISHERS | P=0.551N P=0.059N P=0.339N P=0.349N | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Fibrosis Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 2/42.48 0/39.89 1/40.04 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 4.7% 0.0% 2.5% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- 574 --- 727 (T) |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.607 P=0.258 (e) P=0.515 |(e) (e) (e) (e) |
|POLY 3 | P=0.608 P=0.244 (e) P=0.494 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.605 P=0.239 (e) P=0.493 |(e) (e) (e) (e) |
|POLY 6 | P=0.616 P=0.251 (e) P=0.498 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.611 P=0.239 (e) P=0.515 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.615 P=0.247 (e) P=0.500 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 39
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hematopoietic Cell Proliferation |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 2/50 (4%) 3/50 (6%) 4/50 (8%) |6/50 (12%) 2/50 (4%) 4/50 (8%) 5/50 (10%) |
|POLY-3 RATE (b) | 2/41.32 2/42.41 3/41.55 4/41.80 |6/43.41 2/42.89 4/42.47 5/40.12 |
|POLY-3 PERCENT (g) | 4.8% 4.7% 7.2% 9.6% |13.8% 4.7% 9.4% 12.5% |
|TERMINAL (d) | 0/26 (0%) 1/29 (3%) 0/25 (0%) 0/28 (0%) |3/30 (10%) 2/31 (7%) 0/28 (0%) 1/27 (4%) |
|FIRST INCIDENCE | 707 577 484 352 |406 728 (T) 483 588 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.231 P=0.672N P=0.466 P=0.341 |P=0.419 P=0.133N P=0.403N P=0.555N |
|POLY 3 | P=0.232 P=0.685N P=0.503 P=0.342 |P=0.431 P=0.136N P=0.383N P=0.555N |
|POLY 1.5 | P=0.226 P=0.692N P=0.505 P=0.332 |P=0.437 P=0.135N P=0.380N P=0.547N |
|POLY 6 | P=0.243 P=0.674N P=0.498 P=0.359 |P=0.431 P=0.136N P=0.386N P=0.558N |
|LOGISTIC REGRESSION| P=0.273 P=0.694N P=0.485 P=0.359 |P=0.475 P=0.136N P=0.362N P=0.507N |
|COCH-ARM / FISHERS | P=0.232 P=0.691N P=0.500 P=0.339 |P=0.478 P=0.134N P=0.370N P=0.500N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Spleen |
| Hyperplasia Lymphohistiocytic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 8/50 (16%) |0/50 (0%) 1/50 (2%) 2/50 (4%) 4/50 (8%) |
|POLY-3 RATE (b) | 2/41.22 2/41.96 2/40.24 8/40.07 |0/41.94 1/42.89 2/41.46 4/39.32 |
|POLY-3 PERCENT (g) | 4.9% 4.8% 5.0% 20.0% |0.0% 2.3% 4.8% 10.2% |
|TERMINAL (d) | 2/26 (8%) 1/29 (3%) 1/25 (4%) 7/28 (25%) |0/30 (0%) 1/31 (3%) 2/28 (7%) 4/27 (15%) |
|FIRST INCIDENCE | 727 (T) 715 630 720 |--- 728 (T) 728 (T) 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.007 ** P=0.659N P=0.679 P=0.055 |P=0.019 * P=0.507 P=0.223 P=0.049 * |
|POLY 3 | P=0.004 ** P=0.688N P=0.686 P=0.039 * |P=0.022 * P=0.504 P=0.234 P=0.052 |
|POLY 1.5 | P=0.005 ** P=0.693N P=0.692 P=0.038 * |P=0.023 * P=0.502 P=0.235 P=0.053 |
|POLY 6 | P=0.004 ** P=0.678N P=0.678 P=0.041 * |P=0.022 * P=0.507 P=0.233 P=0.051 |
|LOGISTIC REGRESSION| P=0.005 ** P=0.671N P=0.678 P=0.039 * |(e) P=0.507 P=0.223 P=0.049 * |
|COCH-ARM / FISHERS | P=0.006 ** P=0.691N P=0.691N P=0.046 * |P=0.029 * P=0.500 P=0.247 P=0.059 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 40
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Spleen: Lymphoid Follicle |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 20/50 (40%) 25/50 (50%) 29/50 (58%) 25/50 (50%) |35/50 (70%) 32/50 (64%) 31/50 (62%) 28/50 (56%) |
|POLY-3 RATE (b) | 20/44.80 25/44.28 29/46.10 25/47.39 |35/47.36 32/47.62 31/44.19 28/45.46 |
|POLY-3 PERCENT (g) | 44.7% 56.5% 62.9% 52.8% |73.9% 67.2% 70.2% 61.6% |
|TERMINAL (d) | 12/26 (46%) 20/29 (69%) 16/25 (64%) 14/28 (50%) |23/30 (77%) 21/31 (68%) 23/28 (82%) 16/27 (59%) |
|FIRST INCIDENCE | 503 131 419 120 |191 197 375 111 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.345 P=0.343 P=0.060 P=0.280 |P=0.347N P=0.310N P=0.418N P=0.301N |
|POLY 3 | P=0.445 P=0.178 P=0.056 P=0.282 |P=0.149N P=0.307N P=0.431N P=0.139N |
|POLY 1.5 | P=0.404 P=0.189 P=0.059 P=0.262 |P=0.132N P=0.316N P=0.374N P=0.125N |
|POLY 6 | P=0.480 P=0.172 P=0.049 * P=0.300 |P=0.168N P=0.299N P=0.503N P=0.154N |
|LOGISTIC REGRESSION| P=0.333 P=0.209 P=0.055 P=0.250 |P=0.118N P=0.339N P=0.274N P=0.095N |
|COCH-ARM / FISHERS | P=0.310 P=0.211 P=0.055 P=0.211 |P=0.108N P=0.335N P=0.263N P=0.107N |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 2/40.47 1/40.99 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 4.9% 2.4% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- 561 261 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.344 (e) P=0.227 P=0.492 |(e) (e) (e) (e) |
|POLY 3 | P=0.348 (e) P=0.233 P=0.499 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.345 (e) P=0.236 P=0.496 |(e) (e) (e) (e) |
|POLY 6 | P=0.352 (e) P=0.228 P=0.504 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.432 (e) P=0.235 P=0.638 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.354 (e) P=0.247 P=0.500 |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 41
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Forestomach |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 2/50 (4%) 4/50 (8%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/41.24 2/42.85 4/41.43 1/40.83 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 2.4% 4.7% 9.7% 2.5% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 721 478 484 433 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.519N P=0.507 P=0.162 P=0.743 |(e) (e) (e) (e) |
|POLY 3 | P=0.513N P=0.513 P=0.179 P=0.759 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.517N P=0.505 P=0.181 P=0.755 |(e) (e) (e) (e) |
|POLY 6 | P=0.506N P=0.526 P=0.176 P=0.758N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.444N P=0.505 P=0.173 P=0.740N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.500N P=0.500 P=0.181 P=0.753N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Mineralization |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 1/50 (2%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |
|POLY-3 RATE (b) | 2/41.46 0/41.91 1/39.89 1/40.47 |0/41.94 1/42.89 0/41.46 1/39.32 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 2.5% 2.5% |0.0% 2.3% 0.0% 2.5% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 1/25 (4%) 0/28 (0%) |0/30 (0%) 1/31 (3%) 0/28 (0%) 1/27 (4%) |
|FIRST INCIDENCE | 685 --- 727 (T) 604 |--- 728 (T) --- 728 (T) |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.610N P=0.227N P=0.538N P=0.495N |P=0.432 P=0.507 (e) P=0.479 |
|POLY 3 | P=0.621N P=0.234N P=0.514N P=0.508N |P=0.443 P=0.504 (e) P=0.487 |
|POLY 1.5 | P=0.621N P=0.237N P=0.505N P=0.512N |P=0.445 P=0.502 (e) P=0.489 |
|POLY 6 | P=0.621N P=0.230N P=0.527N P=0.501N |P=0.443 P=0.507 (e) P=0.487 |
|LOGISTIC REGRESSION| P=0.622N P=0.235N P=0.521N P=0.504N |(e) P=0.507 (e) P=0.479 |
|COCH-ARM / FISHERS | P=0.614N P=0.247N P=0.500N P=0.500N |P=0.459 P=0.500 (e) P=0.500 |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 42
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 3/50 (6%) 5/50 (10%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 1/50 (2%) 3/50 (6%) |
|POLY-3 RATE (b) | 1/41.24 3/43.02 5/41.61 2/40.12 |0/41.94 0/42.89 1/41.60 3/40.30 |
|POLY-3 PERCENT (g) | 2.4% 7.0% 12.0% 5.0% |0.0% 0.0% 2.4% 7.4% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 721 533 561 708 |--- --- 691 495 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.585 P=0.327 P=0.094 P=0.501 |P=0.019 * (e) P=0.494 P=0.118 |
|POLY 3 | P=0.568 P=0.320 P=0.102 P=0.490 |P=0.018 * (e) P=0.498 P=0.111 |
|POLY 1.5 | P=0.568 P=0.311 P=0.103 P=0.488 |P=0.018 * (e) P=0.498 P=0.111 |
|POLY 6 | P=0.574 P=0.336 P=0.101 P=0.498 |P=0.018 * (e) P=0.498 P=0.113 |
|LOGISTIC REGRESSION| P=0.605N P=0.307 P=0.101 P=0.500 |P=0.023 * (e) P=0.498 P=0.127 |
|COCH-ARM / FISHERS | P=0.597 P=0.309 P=0.102 P=0.500 |P=0.021 * (e) P=0.500 P=0.121 |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Stomach, Glandular: Epithelium |
| Hyperplasia Focal |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 2/50 (4%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/41.22 0/41.91 2/40.38 1/40.19 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 2.4% 0.0% 5.0% 2.5% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 1/25 (4%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 727 (T) --- 582 689 |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.564 P=0.478N P=0.491 P=0.749N |(e) (e) (e) (e) |
|POLY 3 | P=0.541 P=0.497N P=0.493 P=0.755 |(e) (e) (e) (e) |
|POLY 1.5 | P=0.541 P=0.500N P=0.498 P=0.753 |(e) (e) (e) (e) |
|POLY 6 | P=0.545 P=0.491N P=0.485 P=0.761 |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.550 (e) P=0.497 P=0.759 |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.558 P=0.500N P=0.500 P=0.753N |(e) (e) (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 43
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Testes |
| Cyst |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) | |
|POLY-3 RATE (b) | 0/41.22 0/41.91 2/39.89 0/40.04 | |
|POLY-3 PERCENT (g) | 0.0% 0.0% 5.0% 0.0% | |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 2/25 (8%) 0/28 (0%) | |
|FIRST INCIDENCE | --- --- 727 (T) --- | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.686N (e) P=0.229 (e) | |
|POLY 3 | P=0.708N (e) P=0.229 (e) | |
|POLY 1.5 | P=0.708N (e) P=0.234 (e) | |
|POLY 6 | P=0.705N (e) P=0.222 (e) | |
|LOGISTIC REGRESSION| (e) (e) P=0.229 (e) | |
|COCH-ARM / FISHERS | P=0.695N (e) P=0.247 (e) | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Testes: Germinal Epithelium |
| Atrophy |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 3/50 (6%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |
|POLY-3 RATE (b) | 3/41.42 1/41.95 1/40.05 1/40.83 | |
|POLY-3 PERCENT (g) | 7.2% 2.4% 2.5% 2.5% | |
|TERMINAL (d) | 1/26 (4%) 0/29 (0%) 0/25 (0%) 0/28 (0%) | |
|FIRST INCIDENCE | 685 717 686 433 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.356N P=0.290N P=0.350N P=0.318N | |
|POLY 3 | P=0.345N P=0.300N P=0.317N P=0.310N | |
|POLY 1.5 | P=0.346N P=0.305N P=0.309N P=0.314N | |
|POLY 6 | P=0.343N P=0.292N P=0.328N P=0.302N | |
|LOGISTIC REGRESSION| P=0.339N P=0.290N P=0.323N P=0.297N | |
|COCH-ARM / FISHERS | P=0.339N P=0.309N P=0.309N P=0.309N | |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 44
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Testes: Interstitial Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 5/50 (10%) 0/50 (0%) 1/50 (2%) 2/50 (4%) | |
|POLY-3 RATE (b) | 5/42.79 0/41.91 1/40.05 2/40.39 | |
|POLY-3 PERCENT (g) | 11.7% 0.0% 2.5% 5.0% | |
|TERMINAL (d) | 2/26 (8%) 0/29 (0%) 0/25 (0%) 1/28 (4%) | |
|FIRST INCIDENCE | 519 --- 686 629 | |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.423N P=0.031N* P=0.121N P=0.215N | |
|POLY 3 | P=0.425N P=0.032N* P=0.116N P=0.239N | |
|POLY 1.5 | P=0.424N P=0.032N* P=0.108N P=0.238N | |
|POLY 6 | P=0.424N P=0.031N* P=0.128N P=0.235N | |
|LOGISTIC REGRESSION| P=0.410N P=0.032N* P=0.104N P=0.209N | |
|COCH-ARM / FISHERS | P=0.418N P=0.028N* P=0.102N P=0.218N | |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: C-Cell |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 31/50 (62%) 36/50 (72%) 40/50 (80%) 35/50 (70%) |33/50 (66%) 38/50 (76%) 34/50 (68%) 31/50 (62%) |
|POLY-3 RATE (b) | 31/45.75 36/46.19 40/48.54 35/44.87 |33/46.32 38/47.51 34/46.36 31/42.42 |
|POLY-3 PERCENT (g) | 67.8% 77.9% 82.4% 78.0% |71.3% 80.0% 73.3% 73.1% |
|TERMINAL (d) | 16/26 (62%) 22/29 (76%) 18/25 (72%) 22/28 (79%) |20/30 (67%) 25/31 (81%) 22/28 (79%) 22/27 (82%) |
|FIRST INCIDENCE | 475 313 462 261 |462 197 405 139 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.423 P=0.417 P=0.077 P=0.379 |P=0.496N P=0.319 P=0.398 P=0.503 |
|POLY 3 | P=0.273 P=0.185 P=0.071 P=0.187 |P=0.470N P=0.222 P=0.503 P=0.519 |
|POLY 1.5 | P=0.269 P=0.175 P=0.057 P=0.180 |P=0.381N P=0.216 P=0.501 P=0.588 |
|POLY 6 | P=0.314 P=0.215 P=0.100 P=0.224 |P=0.554 P=0.227 P=0.490 P=0.442 |
|LOGISTIC REGRESSION| P=0.301 P=0.186 P=0.038 * P=0.192 |P=0.310N P=0.197 P=0.482 P=0.558N |
|COCH-ARM / FISHERS | P=0.386 P=0.198 P=0.038 * P=0.263 |P=0.193N P=0.189 P=0.500 P=0.418N |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 45
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Thyroid Gland: Follicle |
| Hyperplasia |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 0/50 (0%) |
|POLY-3 RATE (b) | 0/41.22 0/41.91 0/39.89 1/40.04 |0/41.94 0/42.89 2/41.48 0/39.32 |
|POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% |0.0% 0.0% 4.8% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 1/28 (4%) |0/30 (0%) 0/31 (0%) 1/28 (4%) 0/27 (0%) |
|FIRST INCIDENCE | --- --- --- 727 (T) |--- --- 723 --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.222 (e) (e) P=0.515 |P=0.714N (e) P=0.225 (e) |
|POLY 3 | P=0.210 (e) (e) P=0.494 |P=0.720N (e) P=0.234 (e) |
|POLY 1.5 | P=0.210 (e) (e) P=0.493 |P=0.716N (e) P=0.235 (e) |
|POLY 6 | P=0.211 (e) (e) P=0.498 |P=0.722N (e) P=0.233 (e) |
|LOGISTIC REGRESSION| (e) (e) (e) P=0.515 |P=0.718N (e) P=0.224 (e) |
|COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.695N (e) P=0.247 (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Trachea |
| Inflammation Chronic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 4/50 (8%) |0/50 (0%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 1/41.65 0/41.91 0/39.89 4/41.24 |0/41.94 1/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 2.4% 0.0% 0.0% 9.7% |0.0% 2.3% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 2/28 (7%) |0/30 (0%) 1/31 (3%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 600 --- --- 352 |--- 728 (T) --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.017 * P=0.495N P=0.516N P=0.194 |P=0.605N P=0.507 (e) (e) |
|POLY 3 | P=0.013 * P=0.499N P=0.509N P=0.175 |P=0.585N P=0.504 (e) (e) |
|POLY 1.5 | P=0.013 * P=0.501N P=0.503N P=0.171 |P=0.586N P=0.502 (e) (e) |
|POLY 6 | P=0.014 * P=0.495N P=0.516N P=0.181 |P=0.584N P=0.507 (e) (e) |
|LOGISTIC REGRESSION| P=0.019 * P=0.494N P=0.514N P=0.196 |(e) P=0.507 (e) (e) |
|COCH-ARM / FISHERS | P=0.015 * P=0.500N P=0.500N P=0.181 |P=0.585N P=0.500 (e) (e) |
|=================================================================================================================================|
Date: 06/12/01 EXPERIMENT: 88122 TEST: 06 Page 46
Statistical Analysis of Non-neoplastic Lesions in Rats(FISCHER 344) - ELMIRON
Terminal Sacrifice at 104 weeks
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Urinary Bladder |
| Ulcer |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | 2/50 (4%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |
|POLY-3 RATE (b) | 2/41.46 0/41.91 0/39.89 0/39.19 |0/41.94 0/42.89 0/41.46 0/39.32 |
|POLY-3 PERCENT (g) | 4.8% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 0.0% |
|TERMINAL (d) | 0/26 (0%) 0/29 (0%) 0/25 (0%) 0/28 (0%) |0/30 (0%) 0/31 (0%) 0/28 (0%) 0/27 (0%) |
|FIRST INCIDENCE | 685 --- --- --- |--- --- --- --- |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | P=0.247N P=0.227N P=0.272N P=0.243N |(e) (e) (e) (e) |
|POLY 3 | P=0.242N P=0.234N P=0.245N P=0.249N |(e) (e) (e) (e) |
|POLY 1.5 | P=0.240N P=0.237N P=0.240N P=0.251N |(e) (e) (e) (e) |
|POLY 6 | P=0.244N P=0.230N P=0.254N P=0.245N |(e) (e) (e) (e) |
|LOGISTIC REGRESSION| P=0.246N P=0.235N P=0.245N P=0.248N |(e) (e) (e) (e) |
|COCH-ARM / FISHERS | P=0.241N P=0.247N P=0.247N P=0.253N |(e) (e) (e) (e) |
|=================================================================================================================================|
| | | |
| | Males | Females |
|Dose | 0 MG/KG 14 MG/KG 42 MG/KG 126 |0 MG/KG 28 MG/KG 84 MG/KG 252 |
| | MG/KG | MG/KG |
|=================================================================================================================================|
| |
|Uterus: Endometrium |
| Hyperplasia Cystic |
| |
| |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES | | |
|----------- | | |
|OVERALL (a) | |4/50 (8%) 5/50 (10%) 3/50 (6%) 6/50 (12%) |
|POLY-3 RATE (b) | |4/41.94 5/42.93 3/41.46 6/40.52 |
|POLY-3 PERCENT (g) | |9.5% 11.7% 7.2% 14.8% |
|TERMINAL (d) | |4/30 (13%) 4/31 (13%) 3/28 (11%) 3/27 (11%) |
|FIRST INCIDENCE | |728 (T) 719 728 (T) 273 |
|-------------------| | |
|STATISTICAL TESTS | | |
|-------------------| | |
|LIFE TABLE | |P=0.255 P=0.516 P=0.538N P=0.317 |
|POLY 3 | |P=0.296 P=0.515 P=0.506N P=0.347 |
|POLY 1.5 | |P=0.298 P=0.508 P=0.505N P=0.346 |
|POLY 6 | |P=0.297 P=0.523 P=0.508N P=0.351 |
|LOGISTIC REGRESSION| |P=0.280 P=0.519 P=0.538N P=0.349 |
|COCH-ARM / FISHERS | |P=0.323 P=0.500 P=0.500N P=0.370 |
|=================================================================================================================================|
(a) Number of tumor-bearing animals / number of animals examined at site.
(b) Number of tumor-bearing animals / Poly-3 number
(d) Observed incidence at terminal kill.
(f) Beneath the control incidence are the P-values associated with the trend
test. Beneath the dosed group incidence are the P-values corresponding to
pairwise comparisons between the controls and that dosed group. The life
table analysis regards tumors in animals dying prior to terminal kill as
being (directly or indirectly) the cause of death.
Logistic regression is an alternative
method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage
and Fishers exact tests compare directly the overall incidence rates
For all tests a negative trend is indicated by N
(e) Value of Statistic cannot be computed.
(g) Poly-3 adjusted lifetime tumor incidence.
(I) Interim sacrifice
(T) Terminal sacrifice
# Tumor rates based on number of animals necropsied.
* To the right of any statistical result, indicates significance at (P<=0.05).
** To the right of any statistical result, indicates significance at (P<=0.01).