To assess the efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.
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.
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.
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.
Ulipristal acetate, a selective progesterone receptor modulator, is superior to placebo in achieving amenorrhea and well tolerated for the medical management of symptomatic uterine leiomyomas.
Case Western Reserve School of Medicine, Cleveland, Ohio; Medical University of South Carolina, Charleston, South Carolina; Carolina Women’s Research & Wellness Center, Durham, North Carolina; Willowbend Health & Wellness, Frisco, Texas; Eastern Virginia Medical School, Norfolk, Virginia; Seattle Women’s, Seattle, Washington; Allergan plc, Madison, New Jersey; Allergan plc, Irvine, California; and Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Corresponding author: James H. Liu, MD, Department of Obstetrics and Gynecology, University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, 11100 Euclid Avenue, Cleveland, OH 44106; email: James.Liu@uhhospitals.org.
Supported by Allergan plc (Madison, New Jersey).
Financial Disclosure Dr. Liu is a consultant to Allergan and Pfizer. Dr. Liu is also involved in clinical trials funded by Ferring Pharmaceuticals, AbbVie, Bayer, Palatin, and Allergan. Dr. Soper has been involved in clinical trials funded by AbbVie, Bayer, and Allergan. Dr. Lukes is a consultant for Allergan and has received research grants from Allergan and Watson; received research grants from AbbVie, Myovant, Bayer, and Gynesonics; and has provided consultation support for MyoVant and Abbvie. Dr. Gee is an investigator for this study. Dr. Gee is also involved in clinical trials funded by AbbVie, Bayer, Gynesonics, Myovant, and Obseva. Dr. Kimble is a member of the speakers' bureau for Allergan. Dr. Kroll has received research grants from Allergan, Amneal, Glenmark, Endoceutics, Teva, Izun, and TherapeuticsMD. Dr. Kroll has also received consultant fees from Allergan and AMAG. Dr. Shulman has been involved in speaking, advising, consulting, and educational programs for the following entities: AHM—Advanced Health Media, LLC, Bayer AG, BioPharmX, Inc., Celula, Inc, Connect Healthcare, Inc, Cory Paeth, LLC, Allergan plc, Grey Healthcare Group, Health Advances, LLC, Interpublic Group, IntraMed, Meeting Logistics, LLC, Merck & Co., Inc, Natera, Inc, PharmaWrite, LLC, Previvo Genetics, LLC, Progenity, Inc, Qiagen, Quest Diagnostics Incorporated, Roche Diagnostics Corporation, and Sequenom, Inc. Madhuja Mallick, Anna Chan, Patrick Gillard, Amanda Harrington, and Vilma Sniukiene are current full-time employees of Allergan plc.
Presented in part at the American Society for Reproductive Medicine’s annual meeting, October 28–November 1, 2017, San Antonio, Texas.
Jacqueline Benjamin, PhD, of Prescott Medical Communications Group (Chicago, Illinois) provided medical writing and editorial assistance with financial support from Allergan plc (Madison, New Jersey). Allergan (sponsor) played a role in the study design, conduct, analysis, interpretation, writing of the report, and decision to publish this study.
Each author has indicated that he or she has met the journal's requirements for authorship.
Received November 07, 2017
Received in revised form January 12, 2018
Received in revised form August 01, 2018
Accepted August 09, 2018