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.

Abstract

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.

CLINICAL TRIAL REGISTRATION NUMBERS:

NCT02655224.

JAPIC CLINICAL TRIAL INFORMATION:

JapicCTI-163127.

• Authors: Yutaka Osuga, Kazuaki Enya, Kentarou Kudou, Hiroshi Hoshiai
• Journal: Fertility and sterility (Fertil Steril) Vol. 112 Issue 5 Pg. 922-929.e2 (11 2019) ISSN: 1556-5653 [Electronic] United States
• PMID: 31594635 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Phenylurea Compounds
• Pyrimidinones
• relugolix
• Gonadotropin-Releasing Hormone

Topics

• Administration, Oral
• Adult
• Double-Blind Method
• Female
• Gonadotropin-Releasing Hormone (antagonists & inhibitors)
• Humans
• Japan (epidemiology)
• Leiomyoma (diagnosis, drug therapy, epidemiology)
• Middle Aged
• Pelvic Pain (diagnosis, drug therapy, epidemiology)
• Phenylurea Compounds (administration & dosage)
• Pyrimidinones (administration & dosage)
• Treatment Outcome