To evaluate elagolix, an oral gonadotropin-releasing hormone receptor antagonist, alone or with add-back therapy, in premenopausal women with heavy menstrual bleeding (greater than 80 mL per month) associated with uterine leiomyomas.
This double-blind, randomized, placebo-controlled, parallel-group study evaluated efficacy and safety of elagolix in cohorts 1 (300 mg twice daily) and 2 (600 mg daily) with four arms per cohort: placebo, elagolix alone, elagolix with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate. A sample size of 65 per group was planned to compare elagolix with add-back to placebo on the primary end point: the percentage of women who had less than 80 mL menstrual blood loss and 50% or greater reduction in menstrual blood loss from baseline to the last 28 days of treatment. Safety assessments included changes in bone mineral density.
From April 8, 2013, to December 8, 2015, 571 women were enrolled, 567 were randomized and treated (cohort 1=259; cohort 2=308), and 80% and 75% completed treatment, respectively. Participants had a mean±SD age of 43±5 years (cohort 2, 42±5 years), and 70% were black (cohort 2, 74%). Primary end point responder rates in cohort 1 (cohort 2) were 92% (90%) for elagolix alone, 85% (73%) for elagolix with 0.5 mg estradiol/0.1 mg norethindrone acetate, 79% (82%) for elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate, and 27% (32%) for placebo (all P<.001 vs placebo). Elagolix groups had significant decreases compared with placebo in lumbar spine bone mineral density, which was attenuated by adding 1.0 mg estradiol/0.5 mg norethindrone acetate.
Elagolix with and without add-back significantly reduced menstrual blood loss in women with uterine leiomyomas. Add-back therapy reduced hypoestrogenic effects on bone mineral density.
ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.
University of Texas Southwestern Medical Center, Dallas, Texas; the Mayo Clinic, Rochester, Minnesota; Eastern Virginia Medical School, Norfolk, Virginia; the University of Illinois at Chicago, Chicago, Illinois; Cleveland Clinic, Cleveland, Ohio; Mercy Health Osteoporosis and Bone Health Services, Cincinnati, Ohio; Augusta University, Augusta, Georgia; AbbVie Inc., North Chicago, Illinois; and George Washington University, Washington, DC.
Corresponding author: Bruce R. Carr, MD, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390-9032; email: email@example.com.
AbbVie Inc funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication.
Financial Disclosure Dr. Carr has been a study investigator and received research support from AbbVie and Agile Therapeutics. He also served on the Repros Therapeutics Data and Safety Monitoring Board. Dr. Stewart has been a consultant for AbbVie, Allergan, Astellas, Bayer, Gynesonics, Myovant, and Welltwigs. She has received research support from the National Institutes for Health (HS023418) and holds a patent for Methods and Compounds for Treatment of Abnormal Uterine Bleeding (US 6440445). Dr. Archer has received research support from AbbVie, TherapeuticsMD, Bayer HealthCare, Endoceutics, Glenmark, Shionogi, Symbio, and Radius. He has been a consultant to AbbVie, TherapeuticsMD, Bayer HealthCare, Endoceutics, Agile Pharmaceuticals, Exeltis/CHEMO France, and TEVA/HR Pharma. Dr. Al-Hendy has been a consultant to Abbvie, Bayer, Allergan, and MD Stem Cells. He has received research support, National Institute of Health (R01 ES 028615-01, R01HD 087417, R01 HD 094378, R01 HD 094380), and holds a patent for methods for novel diagnostics and therapeutics for uterine sarcoma (US Patent No. 9,790,562 B2). Dr. Bradley has been an advisor to Medtronic, AbbVie, Allergan, PCORI, Bayer, Boston Scientific, and Female Health. She has been a speaker for Bayer, Smith & Nephew, and Karl Storz and served on the Data Safety and Monitoring Board of Gynesonics. She received research support from Bayer and royalties as author/editor for Elsevier, Wolters Kluwer, and UpToDate. Dr. Watts has been a speaker for Amgen, Radius, and Shire and has been a consultant to AbbVie, Amgen, Radius, and Sanofi. He is the owner of OsteoDynamics. Dr. Diamond has received research support from Abbvie Inc, Bayer Healthcare, and ObsEva. He is a stockholder and serves on the Board of Directors of Advanced Reproductive Care. Dr. Gao is a former employee of AbbVie Inc and a current employee of Gilead Sciences. Drs. Owens, Chwalisz, Duan, Soliman, and Dufek are employees with stock/stock options in AbbVie, Inc. Dr. Simon has received research support from AbbVie Inc, Actavis, Agile Therapeutics, Bayer Healthcare, New England Research Institute, Novo Nordisk, Palatin Technologies, Symbio Research, and TherapeuticsMD. He has been a speaker for Amgen, Eisai, Merck, Noven Pharmaceuticals, Novo Nordisk, and Shionogi. He has been an advisor and/or consultant for AbbVie Inc, AMAG Pharmaceuticals, Amgen, Apotex, Ascend Therapeutics, JDS Therapeutics, Merck & Co, Noven Pharmaceuticals, Novo Nordisk, Nuelle, Perrigo Company, Radius Health, Regeneron Pharmaceutical, Sanofi SA, Sermonix Pharmaceuticals, Shionogi, Sprout Pharmaceuticals, Symbiotec Pharmalab, and TherapeuticsMD. He is a stockholder in Sermonix Pharmaceuticals.
Presented at the 65th Annual Clinical and Scientific Meeting of the American College of Obstetricians and Gynecologists, May 6–9, 2017, San Diego, California; the 3rd Congress of the Society of Endometriosis and Uterine Disorders, April 6–8, 2017, Singapore; the 73rd Annual Meeting of the American Society for Reproductive Medicine, October 28–November 1, 2017, San Antonio, Texas; and the 46th AAGL Global Congress on Minimally Invasive Gynecology, November 12–16, 2017, National Harbor, Maryland.
The authors thank all of the trial investigators and the women who participated in this clinical trial. Jane Rodgers, PhD, and Jeanie K. Meckes, PhD, of AbbVie Inc., provided medical writing assistance.
Each author has indicated that he or she has met the journal’s requirements for authorship.
Received May 11, 2018
Received in revised form July 30, 2018
Accepted August 08, 2018