Objective: To evaluate the efficacy and safety of three dose levels of relugolix, a gonadotropin-releasing hormone receptor antagonist, compared with placebo and leuprorelin in women with endometriosis-associated pain.

Design: Phase 2, multicenter, randomized, double-blind, placebo-controlled study.

Setting: Hospitals and clinics.

Patient(s): Adult premenopausal women with endometriosis who had dysmenorrhea and endometriosis-associated pelvic pain.

Intervention(s): During a 12-week treatment period, patients received relugolix 10 mg (n = 103), 20 mg (n = 100), or 40 mg (n = 103) as a daily oral dose; placebo (n = 97) as a daily oral dose; or leuprorelin 3.75 mg (n = 80) as a monthly subcutaneous injection.

Main outcome measure(s): Primary endpoint was the change from baseline in mean visual analog scale score for pelvic pain during 28 days before the end of treatment.

Result(s): The mean changes in mean visual analog scale score for pelvic pain were -3.8 mm in the placebo group; -6.2, -8.1, and -10.4 mm in the relugolix 10-mg, 20-mg, and 40-mg groups; respectively; and -10.6 mm in the leuprorelin group. The major adverse events with relugolix were hot flush, metrorrhagia, menorrhagia, and irregular menstruation, and bone mineral density decrease in a dose-response manner, which were also observed in the leuprorelin group with a frequency comparable with that in the relugolix 40-mg group.

Conclusion(s): Oral administration of relugolix alleviated endometriosis-associated pain in a dose-response manner and was generally well tolerated. Relugolix 40 mg demonstrated efficacy and safety comparable with those of leuprorelin.

Clinical trial registration number: NCT01458301.