Objective: To assess the efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.
Methods: This phase 3, double-blind, double-dummy, placebo-controlled trial randomized premenopausal women (18-50 years) with uterine leiomyomas and abnormal uterine bleeding to once-daily 5 mg ulipristal, 10 mg ulipristal, or placebo in two 12-week treatment courses separated by a drug-free interval of two menses. Coprimary end points were rates of and time to amenorrhea during course 1. Change from baseline to end of course 1 in the Revised Activities subscale of the Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire was a secondary end point. A sample size of 400 was planned to compare separately each ulipristal dose with placebo.
Results: From January 2014 through November 2016, 432 women were randomized. Demographic characteristics were similar across treatment groups. In course 1, 68 of 162 (42.0% [97.5% CI 33.3-51.1]) and 86 of 157 (54.8% [97.5% CI 45.5-63.8]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 0 of 113 (0.0% [97.5% CI 0.0-3.8]) patients treated with placebo achieved amenorrhea (P<.001 for each dose); most women who achieved amenorrhea did so within 10 days (time to amenorrhea, P<.001 for each dose). Significantly greater improvements in Uterine Fibroid Symptom and Health-Related Quality of Life Revised Activities subscale scores were reported with 5 mg and 10 mg ulipristal compared with placebo (least squares mean change from baseline: 48.3, 56.7, and 13.0, respectively; P<.001 for each dose). Both ulipristal doses were well tolerated; in course 1, hot flush occurred in 7.5%, 11.6%, and 1.7% of patients treated with 5 mg ulipristal, 10 mg ulipristal, and placebo, respectively.
Conclusion: Treatment with 5 mg or 10 mg ulipristal was superior to placebo in achieving amenorrhea and generally well tolerated for the medical management of symptomatic uterine leiomyomas.
Clinical trial registration: ClinicalTrials.gov, NCT02147158.