Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas: A Randomized Controlled Trial

Abstract

Objective: To assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.

Methods: This phase 3, double-blind, placebo-controlled study enrolled premenopausal women (aged 18-50 years) with abnormal uterine bleeding, one or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. Patients were randomized 1:1:1 to 5 mg ulipristal, 10 mg ulipristal, or placebo once daily for 12 weeks followed by 12-week drug-free follow-up. Coprimary endpoints were rate of and time to amenorrhea, defined as no bleeding for the last 35 consecutive days of treatment. Secondary endpoints included rates of amenorrhea from day 11 and change from baseline to endpoint in the Revised Activities subscale of the Uterine Fibroid Symptom and Quality of Life questionnaire, which includes questions pertaining to physical and social activities. Safety assessments included adverse event monitoring and endometrial biopsies. A sample size of 150 was planned to compare separately each dose of ulipristal with placebo.

Results: From March 2014 to March 2016, 157 patients were randomized. Demographics were similar across treatment groups. Amenorrhea was achieved by 25 of 53 (47.2% [97.5% CI 31.6-63.2]) and 28 of 48 (58.3% [97.5% CI 41.2-74.1]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 1 of 56 (1.8% [97.5% CI 0.0-10.9]) placebo-treated patients (both P<.001). Time to amenorrhea was shorter for both ulipristal doses compared with placebo (P<.001), and both doses of ulipristal resulted in improved quality of life compared with placebo (P<.001). Common adverse events (5% or greater in either ulipristal group during treatment) were hypertension, elevated blood creatinine phosphokinase, and hot flushes. Serious adverse events occurred in four patients, but none was considered related to treatment. Endometrial biopsies were benign.

Conclusion: Ulipristal at 5 mg and 10 mg were well tolerated and superior to placebo in rate of and time to amenorrhea in women with symptomatic uterine leiomyomas.

Clinical trial registration: Clinicaltrials.gov number, NCT02147197.

Figures

Fig. 1.

Study design. Orange dots and lines represent the commencement and continuation of menses, respectively. S, screening; V, visit. Simon. Ulipristal Acetate for Uterine Leiomyomas. Obstet Gynecol 2018.

Fig. 2.

Patient disposition. Gray boxes indicate placebo, green boxes indicate ulipristal acetate (UPA) 5 mg, and blue boxes indicate UPA 10 mg. Simon. Ulipristal Acetate for Uterine Leiomyomas. Obstet Gynecol 2018.

Fig. 3.

Time to amenorrhea (intent-to-treat population). Hazard ratio (97.5% CI) for 5 mg ulipristal acetate (UPA) and 10 mg UPA, 35.5 (3.6–348.5) and 49.1 (5.0–480.9), respectively, *Log-rank P<.001 vs placebo. Time to amenorrhea was analyzed using log-rank tests. Simon. Ulipristal Acetate for Uterine Leiomyomas. Obstet Gynecol 2018.

Fig. 4.

Change from baseline at end of treatment in Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire (UFS-QOL) scores (intent-to-treat population). *P<.01, †P<.001 vs placebo. Error bars represent standard error. Analysis of covariance controlling for baseline score and pooled study site was used for change from baseline in UFS-QOL scores. Health-Related Quality of Life (HRQOL) Total score and HRQOL subscale scores range from 0 to 100; higher scores indicate better HRQOL. Symptom severity subscale score ranges from 0 to 100; higher scores indicate greater symptom severity. UPA, ulipristal acetate.