Relugolix, an oral gonadotropin-releasing hormone receptor antagonist, reduces endometriosis-associated pain in a dose–response manner: a randomized, double-blind, placebo-controlled study

ObjectiveTo 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.DesignPhase 2, multicenter, randomized, double-blind, placebo-controlled study.SettingHospitals 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 NumberNCT01458301. 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. Phase 2, multicenter, randomized, double-blind, placebo-controlled study. Hospitals and clinics. Adult premenopausal women with endometriosis who had dysmenorrhea and endometriosis-associated pelvic pain. 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. Primary endpoint was the change from baseline in mean visual analog scale score for pelvic pain during 28 days before the end of treatment. 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. 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.