O-251 Treatment of endometriosis-associated pain with merigolix, an oral GnRH receptor antagonist: results from a phase 2a, randomized, double-blind, placebo-controlled study

Abstract Study question Does merigolix administered orally once daily for 12 weeks reduce the pain symptoms in women with endometriosis-associated pains (EAP)? Summary answer Merigolix was effective in improving endometriosis-associated pains at 12-week treatment, with no serious side effect and favorable bone mineral density profile. What is known already Suppression of estradiol can improve estrogen-dependent diseases such as endometriosis. Merigolix is an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) receptor antagonist with dose-dependent estradiol suppression in a Phase I clinical trial of healthy premenopausal women. Study design, size, duration This was a multi-center, randomized, double-blind, placebo-controlled Phase 2a study to evaluate the efficacy and safety of merigolix in women with moderate to severe EAP. Treatment was administered orally once daily for 12 weeks. Participants/materials, setting, methods In this trial, 86 subjects with surgically diagnosed and moderate to severe EAP were randomized to merigolix 120 mg or 240 mg or 320 mg or placebo. Pain was measured daily on a numeric rating scale of 11-point and recorded in an electronic diary. The primary endpoint was the mean changes of dysmenorrhea at week 12, and the secondary endpoints included the change of non-menstrual pelvic pain (NMPP). Main results and the role of chance Total 86 subjects were randomized to merigolix 120 mg (n = 20), 240 mg (n = 21), 320 mg (n = 22), or placebo (n = 23). A total of 86.0% completed the treatment period, with relatively higher discontinuation rate in the placebo group. The mean change of dysmenorrhea score at week 12 showed significant reduction with all merigolix doses compared to placebo (p < 0.05). A significant reduction for NMPP was observed for merigolix 320mg (p = 0.007) against placebo. Treatment of merigolix 240mg and 320 mg reduced dyspareunia significantly compared to placebo (p < 0.05). Women treated with merigolix experienced a higher incidence of hot flushes compared to placebo. No clinically significant changes in spinal bone mineral density were observed at Week 12 in all dose groups (<-2.2%). Limitations, reasons for caution We report data of 3-Month treatment. A future long-term study for Month 6 will provide more robust information on the risks of bone loss and sustained effect. Wider implications of the findings The merigolix 320mg group definitely provided substantial improvement in EAP symptoms. The 120mg dose did not achieve significant reduction in NMPP in this small-scale trial, anticipating better efficacy in a larger study. Trial registration number Yes