Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial

Bruce R Carr, Elizabeth A. Stewart, David F. Archer, Ayman Al-Hendy, Linda Bradley, Nelson B. Watts, Michael P. Diamond, Jingjing Gao, Charlotte D. Owens, Kristof Chwalisz, W. Rachel Duan, Ahmed M. Soliman, Matthew B. Dufek, James A. Simon

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9 Scopus citations

Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.

Original languageEnglish (US)
Pages (from-to)1252-1264
Number of pages13
JournalObstetrics and Gynecology
Volume132
Issue number5
DOIs
StatePublished - Nov 1 2018

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Carr, B. R., Stewart, E. A., Archer, D. F., Al-Hendy, A., Bradley, L., Watts, N. B., Diamond, M. P., Gao, J., Owens, C. D., Chwalisz, K., Duan, W. R., Soliman, A. M., Dufek, M. B., & Simon, J. A. (2018). Elagolix Alone or With Add-Back Therapy in Women With Heavy Menstrual Bleeding and Uterine Leiomyomas: A Randomized Controlled Trial. Obstetrics and Gynecology, 132(5), 1252-1264. https://doi.org/10.1097/AOG.0000000000002933