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.