Volume 108, Issue 1, Pages 152–160.e4
Authors:
David F. Archer, M.D., Elizabeth A. Stewart, M.D., Rita I. Jain, M.D., Robert A. Feldman, M.D., Andrea S. Lukes, M.D., Janine D. North, B.S., Ahmed M. Soliman, Ph.D., Jingjing Gao, Ph.D., Juki W. Ng, Pharm.D., Ph.D., Kristof Chwalisz, M.D., Ph.D.
Abstract:
Objective
To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E2/progestogen add-back therapy.
Design
Proof-of-concept, dose-ranging, multiple-cohort study.
Setting
Forty-five US clinics.
Patient(s)
Premenopausal women with fibroids and heavy menstrual bleeding (menstrual blood loss [MBL] >80 mL per cycle).
Intervention(s)
Three months' treatment with elagolix alone: 100 mg twice daily (BID), 200 mg BID, 300 mg BID, 400 mg once daily (QD), or 600 mg QD (all but the 600 mg QD arm were placebo controlled); or elagolix plus add-back therapy: 200 mg BID plus continuous low-dose E2 0.5 mg/norethindrone acetate 0.1 mg or elagolix 300 mg BID plus E2 1 mg continuously and cyclical P 200 mg.
Main Outcome Measure(s)
Least-squares mean percentage change in MBL; adverse events (AEs).
Result(s)
Mean age was 41.8 years; 73.8% were black; mean baseline MBL was 267 mL. Of randomized women (elagolix alone, n = 160; placebo, n = 50; elagolix with add-back therapy, n = 61), 228 of 271 completed the 3-month treatment period. The MBL percentage change from baseline to last 28 days was significantly greater with elagolix alone (range, −72% to −98%; dose-dependent reduction was highest with 300 mg BID) vs. placebo (range, −8% to −41%); mean percentage changes with add-back regimens were −80% to −85%. Overall AEs were dose independent (elagolix alone, 70.0%–81.3%) but lower with placebo (56.0%) and add-back regimens (55.6%–70.6%). Hot flush was the most common AE (elagolix alone, 45.5%–62.5%; placebo, 12.0%; add-back regimens, 18.5%–26.5%).
Conclusion(s)
Elagolix significantly reduced heavy menstrual bleeding in women with fibroids. Low-dose add-back regimens substantially reduced flushing.
