Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist: Results from a Phase 2, Randomized Controlled Study

Abstract

Purpose Elagolix is a novel, oral GnRH antagonist that dose-dependently suppresses estradiol levels. This study evaluated safety and efficacy of elagolix vs. leuprorelin acetate (LA) and placebo in women with endometriosis-associated pain. Methods In this multicenter, double-blind study, women with laparoscopically confirmed endometriosis were randomized to oral elagolix 150 or 250 mg once daily, placebo or 3.75 mg LA intramuscularly (i.m.) monthly for 12 weeks. Placebo and LA patients were re-randomized to elagolix, and elagolix patients continued treatment for another 12 weeks. Results Baseline demographics were similar among groups (mean age 31.7 years). Significantly greater reductions in monthly mean pelvic pain compared with placebo (p<0.05) were observed in both elagolix doses at week 4, elagolix 250 mg at week 8 and LA at weeks 4, 8 and 12. The mean (95% CI) percentage change in spinal bone mineral density (BMD) from baseline at week 12 was -1.05 (-1.68, -0.43), -0.80 (-1.53, -0.07) and -1.63 (-2.28, -0.99) for elagolix 150-mg, 250-mg and LA groups, respectively, compared with a mean percentage increase in placebo group (0.11 [-0.50, 0.71]). Headache was the most common adverse event for all treatment groups. Conclusions Both elagolix and LA reduced endometriosis-associated pain for up to 24 weeks of treatment and were associated with generally acceptable safety profiles in this study. Based on relatively small changes from baseline to week 12 in BMD, elagolix may offer a potential long-term treatment option for endometriosis-associated pain in affected women. Larger clinical studies with elagolix are warranted. Trial Registration Clinicaltrials.gov Identifier: NCT00797225.