Elagolix for the management of heavy menstrual bleeding associated with uterine fibroids: results from a phase 2a proof-of-concept study

Objective To evaluate the safety and efficacy of elagolix vs. placebo and elagolix with low-dose E 2 /progestogen add-back therapy. Design Proof-of-concept, dose-ranging, multiple-cohort study. Setting 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 E 2 0.5 mg/norethindrone acetate 0.1 mg or elagolix 300 mg BID plus E 2 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. Clinical Trial Registration Number NCT01441635.