Relugolix, a novel oral gonadotropin-releasing hormone antagonist, in the treatment of pain symptoms associated with uterine fibroids: a randomized, placebo-controlled, phase 3 study in Japanese women

Objective: To investigate the efficacy and safety of the oral gonadotropin-releasing hormone receptor antagonist, relugolix, in patients experiencing uterine fibroid-associated pain. Design: Phase 3, multicenter, randomized, double-blind, placebo-controlled study. Setting: Medical centers. Patient(s): Premenopausal Japanese women (N = 65) experiencing moderate-to-severe uterine fibroid-associated pain with a maximum Numerical Rating Scale (NRS) score of >= 4 were randomized and completed the study. Intervention(s): Once-daily 40 mg relugolix (n = 33) or placebo (n = 32) for 12 weeks. Main Outcome Measure(s): Primary end point: proportion of patients with a maximum NRS score of <= 1 during the 28-day period before the final dose of study drug. Secondary end points: proportion of patients with no pain (NRS = 0) and percentage of days without pain during the 28-day period before the final dose of study drug; adverse events. Result(s): More patients receiving relugolix versus placebo achieved a maximum NRS score of <= 1 during the 28-day period before the final dose of study drug (57.6% vs. 3.1%). Similarly, more patients receiving relugolix versus placebo achieved a maximum NRS score of 0 (48.5% vs. 3.1%) and experienced more days without pain (96.4% vs. 71.4%). More patients receiving relugolix versus placebo experienced treatment-emergent adverse events (TEAEs; 87.9% vs. 56.3%); however, the rate of treatment discontinuation was low and not different between groups. Most TEAEs were mild to moderate in intensity. TEAEs (>= 10%) included hot flush, metrorrhagia, hyperhidrosis, and menorrhagia, consistent with relugolix's mechanism of action, and viral upper respiratory tract infection. Conclusion(s): Relugolix improved uterine fibroid-associated pain and was well tolerated. (C) 2019 The Authors. Published by Elsevier Inc. on behalf of the American Society for Reproductive Medicine.