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

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.

• Authors: 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
• Journal: Obstetrics and gynecology (Obstet Gynecol) Vol. 132 Issue 5 Pg. 1252-1264 (11 2018) ISSN: 1873-233X [Electronic] United States
• PMID: 30303923 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Contraceptive Agents, Female
• Estrogens
• Hemoglobins
• Hydrocarbons, Fluorinated
• Pyrimidines
• Gonadotropin-Releasing Hormone
• Estradiol
• elagolix
• Norethindrone Acetate

Topics

• Adult
• Contraceptive Agents, Female (administration & dosage)
• Double-Blind Method
• Drug Therapy, Combination
• Estradiol (administration & dosage)
• Estrogens (administration & dosage)
• Female
• Gonadotropin-Releasing Hormone (antagonists & inhibitors)
• Hemoglobins (metabolism)
• Humans
• Hydrocarbons, Fluorinated (adverse effects, therapeutic use)
• Leiomyoma (complications, drug therapy, pathology)
• Menorrhagia (blood, drug therapy, etiology)
• Middle Aged
• Norethindrone Acetate (administration & dosage)
• Pyrimidines (adverse effects, therapeutic use)
• Quality of Life
• Tumor Burden (drug effects)
• Uterine Neoplasms (complications, drug therapy, pathology)