human urine following administration of radiolabeled NGM. These include 18, 19-Dinor-17-pregn-4-en-20-yn-3-one,17-hydroxy-13-ethyl,(17α)-(-);18,19-Dinor-5β-17-pregnan-20-yn,3α,17β-dihydroxy-13-ethyl,(17α), various hydroxylated metabolites and conjugates of these metabolites.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility[See Warnings and Precautions (5.2, 5.10) and Use in Specific Populations (8.1).]
14 CLINICAL STUDIES
14.1 ContraceptionIn three US clinical trials with ORTHO-CYCLEN, 1,651 women aged 18 to 38 years were studied for up to 24 cycles, proving a total of 24,272 cycles of exposure. The racial demographic was about 73–86% Caucasian, 8–13% African-American, 6–14% Hispanic with the remainder Asian or Other (≤1%). There were no exclusions on the basis of weight; the weight range for women treated was 82–303 lbs, with a mean weight of about 135 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
In four clinical trials with ORTHO TRI-CYCLEN, 4,756 women aged 15 to 41 years were studied for 24 cycles, providing a total of 45,244 cycles of exposure. The racial demographic was about 87–90% Caucasian, 6–10% African-American, with the remainder Asian (≤1%) or Other (2–5%). There were no exclusions on the basis of weight; the weight range for women treated was 80–310 lbs, with a mean weight of about 132 lbs. The pregnancy rate was approximately 1 pregnancy per 100 women-years.
14.2 AcneORTHO TRI-CYCLEN was eva luated for the treatment of acne vulgaris in two randomized, double-blind, placebo-controlled, multicenter, six- (28 day) cycle studies. Two hundred twenty-one patients received ORTHO TRI-CYCLEN and 234 patients received placebo. Mean age at enrollment for both groups was 28 years. At the end of 6 months, the mean total lesion count changed from 55 to 31 (42% reduction) in patients treated with ORTHO TRI-CYCLEN and from 54 to 38 (27% reduction) in patients similarly treated with placebo. Table 4 summarizes the changes in lesion count for each type of lesion. Based on the investigator's global assessment conducted at the final visit, patients treated with ORTHO TRI-CYCLEN showed a statistically significant improvement in total lesions compared to those treated with placebo.
Table 4: Acne Vulgaris Indication. Combined Results: Two Multicenter, Placebo-Controlled Trials. Observed Means at Six Months (LOCF)* and at Baseline. Intent-to-Treat Population. ORTHO TRI-CYCLEN
(N=221) Placebo
(N=234) Difference in Counts between ORTHO TRI-CYCLEN and Placebo at 6 Months
# of Lesions Counts % Reduction Counts % Reduction
* LOCF: Last Observation Carried Forward
INFLAMMATORY LESIONS
Baseline Mean 19 19
Sixth Month Mean 10 48% 13 30% 3 (95% CI: -1.2, 5.1)
NON-INFLAMMATORY LESIONS
Baseline Mean 36 35
Sixth Month Mean 22 34% 25 21% 3 (95% CI: -0.2, 7.8)
TOTAL LESIONS
Baseline Mean 55 54 7 (95% CI: 2.0, 11.9)
Sixth Month Mean 31 42% 38 27%
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
ORTHO-CYCLEN
ORTHO-CYCLEN Tablets are available in a blister card with a DIA
