To assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.
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.
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.
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.
Clinicaltrials.gov number, NCT02147197.
Ulipristal acetate, a selective progesterone receptor modulator, is well-tolerated and superior to placebo for the treatment of abnormal uterine bleeding associated with uterine leiomyomas.
George Washington University School of Medicine, Women's Health & Research Consultants, Washington, DC; Uniformed Services University of the Health Sciences, Bethesda, Maryland; Johns Hopkins University School of Medicine, Baltimore, Maryland; Allergan plc, Madison, New Jersey; and Augusta University, Augusta, Georgia.
Corresponding author: James A. Simon, MD, Women's Health & Research Consultants, 1850 M Street, NW #450, Washington, DC 20036; email: jsimon@JamesASimonMD.com.
Sponsored by Allergan plc (Madison, New Jersey). Writing and editorial assistance were provided by Jennifer C. Jaworski, MS, and Wendy J. van der Spuy, PhD, of Prescott Medical Communications Group, Inc (Chicago, Illinois) with support from Allergan plc (Jersey City, New Jersey). Allergan (sponsor) played a role in the study design, conduct, analysis, interpretation, writing of the report, and the decision to publish this study.
Financial Disclosure Dr. Simon served (in the past year, or current) as a consultant/advisor to AbbVie, Inc, Allergan, Plc, AMAG Pharmaceuticals, Inc, Ascend Therapeutics, Azure Biotech, Inc, Millendo Therapeutics, Inc, Nuelle, Inc, Radius Health, Inc, Regeneron Pharmaceuticals, Inc, Roivant Sciences, Inc, Sanofi SA, Sebela Pharmaceuticals, Inc, Sermonix Pharmaceuticals, Inc, Shionogi Inc, Symbiotec Pharmalab, TherapeuticsMD, and Valeant Pharmaceuticals; on the speakers' bureaus of Novo Nordisk, Shionogi Inc, and Valeant Pharmaceuticals; received grant/research support from AbbVie, Inc, Allergan, Plc, Agile Therapeutics, Bayer Healthcare LLC, New England Research Institute, Inc, ObsEva SA, Palatin Technologies, Symbio Research, Inc, and TherapeuticsMD; and is a stockholder by direct purchase in Sermonix Pharmaceuticals. Dr. Catherino is a consultant of AbbVie, Inc, Allergan plc, and Bayer. Dr. Segars served as a consultant for Bayer and has received grant/research support from Biospecifics, Inc. Drs. Blakesley, Chan, and Sniukiene are current full-time employees of Allergan plc. Dr. Al-Hendy is a consultant for AbbVie, Allergan plc, Bayer, Myovant, and Repros.
Presented in part at the American Society for Reproductive Medicine Annual Meeting, October 16–20, 2016, Salt Lake City, Utah; the 106th Annual Meeting of the United States and Canadian Academy of Pathology, March 4–10, 2017, San Antonio, Texas; the 64th Annual Scientific Meeting of the Society for Reproductive Investigation, March 15–18, 2017, Orlando, Florida; and the Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists, May 6–9, 2017, San Diego, California.
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