Results from pooled Phase III studies of ulipristal acetate for emergency contraception

Abstract

Background

Ulipristal acetate (UPA) is a new effective option to prevent unintended pregnancies up to 5 days after unprotected intercourse. We used pooled data from two Phase III studies to refine our understanding of the efficacy of UPA by time from unprotected intercourse and the effects of other factors on pregnancy rates.

Study Design

Data from two Phase III studies were pooled to create a larger analysis population. Analyses were performed on the first participation of 2183 women.

Results

A total of 41 women became pregnant despite the use of UPA, yielding an overall proportion pregnant of 1.9% (1.3%–2.5%). Proportions of pregnant women were higher among those with further acts of unprotected intercourse in the same cycle and among obese women. These varied from 1.3% (0.9%–2.0%) among nonobese women who had no further acts of unprotected intercourse (n= 1704) to 8.3% (0.2%–38.5%) among obese women who had subsequent unprotected intercourse (n= 12).

Conclusions

UPA is effective and safe in preventing pregnancy after unprotected intercourse. Its effectiveness is lower among women who have subsequent unprotected intercourse and among obese women.

Introduction

Emergency contraception (EC) is used as a contraceptive backup option to reduce the risk of pregnancy following unprotected intercourse (UPI). Combined treatment with ethinyl estradiol and levonorgestrel (LNG) has been replaced by treatment with LNG alone because it is more effective [1]. However, clinical trials have shown that the efficacy of LNG has very limited, if any, effectiveness if taken beyond 96 h after sexual intercourse [2], falling short of covering the 5-day lifespan of sperm in the female genital tract. Until recently, the only available method consistently effective 5 days after intercourse was the insertion of a copper intrauterine device (IUD) [3], although its use has been very limited by the need for insertion by a skilled health care professional and misperceptions about IUDs among women. Recent development in EC pharmacology in the form of a progesterone receptor modulator pill [ulipristal acetate (UPA)] provides a new effective option to prevent unintended pregnancies, encompassing the 5-day period that sperm can survive in the female genital tract. Based on the results of two large-scale Phase III studies designed to provide statistical evidence that UPA is effective for EC up to 120 h after intercourse [4], [5], UPA was approved by the European Medicines Agency (EMA) in 2009 (brand name ellaOne) and by the Food and Drug Administration in 2010 (brand name ella) as a safe and effective method of EC for use up to 5 days after unprotected sexual intercourse. A meta-analysis consisting of two pooled randomized efficacy trials that included a LNG comparison group also showed that in comparison with LNG, UPA significantly reduced the risk of becoming pregnant, whether used within 72 h [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.33–0.99) or 24 h (OR, 0.35; 95% CI, 0.11–0.93) or 120 h (OR, 0.55; 95% CI, 0.32–0.93) after unprotected sexual intercourse [5]. Based on these results, the EMA changed the product license to indicate superior efficacy of UPA over LNG EC. The same study showed that UPA seemed to be as well tolerated as LNG and was associated with no greater risk of menstrual disturbance.

To refine our estimates of the efficacy of UPA by time from UPI and explore the effects of other factors on the probability of pregnancy, we use pooled data from the two Phase III studies conducted to study UPA 30 mg for EC, which provide better generalizability of results by diversifying the sociodemographic composition of the sample including women from three countries and increases statistical power of the analysis.