e.
Excretion
The terminal half-life of ulipristal acetate in plasma following a single 30 mg dose is estimated to 32.4 ± 6.3 hours.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity: Carcinogenicity studies with ulipristal acetate have not been conducted.
Genotoxicity: Ulipristal acetate was not genotoxic in the Ames assay, in vitro mammalian assays utilizing mouse lymphoma cells and human peripheral blood lymphocytes, and in an in vivo micronucleus assay in mice.
Impairment of Fertility: Single oral doses of ulipristal acetate prevented ovulation in 50% of rats at 2 times the human exposure based on body surface area (mg/m2). Single doses of ulipristal acetate given on post-coital days 4 or 5 prevented pregnancy in 80-100% of rats and in 50% of rabbits when given on post-coital days 5 or 6 at drug exposures 4 and 12 times the human exposure based on body surface area. Lower doses administered for 4 days to rats and rabbits were also effective at preventing ovulation and pregnancy.
14 CLINICAL STUDIES
Two multicenter clinical studies eva luated the efficacy and safety of ella. An open-label study provided the primary data to support the efficacy and safety of ulipristal acetate for emergency contraception when taken 48 to 120 hours after unprotected intercourse. A single-blind comparative study provided the primary data to support the efficacy and safety of ulipristal acetate for emergency contraception when taken 0 to 72 hours after unprotected intercourse and provided supportive data for ulipristal acetate for emergency contraception when taken > 72 to 120 hours after unprotected intercourse. Women in both studies were required to have a negative pregnancy test prior to receiving emergency contraception. The primary efficacy analyses were performed on subjects less than 36 years of age who had a known pregnancy status after taking study medication.
Table 3: Summary of Clinical Trial Results for Women Who Received a Single Dose of ella (30 mg Ulipristal Acetate)
Open-Label Study
48 to 120 Hours*
Single-Blind Comparative Study
0 to 72 Hours*
N = 1,242
N = 844
Expected Pregnancy Rate**
5.5
5.6
Observed Pregnancy Rate**
(95% confidence interval)
2.2
(1.5, 3.2)
1.9
(1.1, 3.1)
* Time after unprotected intercourse when ella was taken
**Number of pregnancies per 100 women at risk for pregnancy
14.1 Open-Label Study
This study was a multicenter open-label trial conducted at 40 family planning clinics in the United States. Healthy women with a mean age of 24 years who requested emergency contraception 48 to 120 hours after unprotected intercourse received a dose of 30 mg ulipristal acetate (ella). The median BMI for the study subjects was 25.3 and ranged from 16.1 to 61.3 kg/m2.
Twenty-seven pregnancies occurred in 1,242 women aged 18 to 35 years eva luated for efficacy. The number of pregnancies expected without emergency contraception was calculated based on the timing of intercourse with regard to each woman’s menstrual cycle. ella statistically significantly reduced the pregnancy rate, from an expected rate of 5.5% to an observed rate of 2.2%, when taken 48 to 120 hours after unprotected intercourse.
14.2 Single-Blind Comparative Study
This study was a multicenter, single-blind, randomized comparison of the efficacy and sa
