Relugolix for oral treatment of uterine leiomyomas: a dose-finding, randomized, controlled trial.

Abstract

BACKGROUND:

Uterine leiomyomas are the most common neoplasm affecting women and frequently cause heavy menstrual bleeding and pain. Gonadotropin-releasing hormone (GnRH) receptor antagonists provide fast symptom relief and show promise as a medical (non-surgical) treatment option and as a presurgical treatment to reduce leiomyoma size. The aim of this study was to evaluate the efficacy and safety of three dose levels of oral relugolix, a small molecule GnRH receptor antagonist, in Japanese women with uterine leiomyomas and heavy menstrual bleeding.

METHODS:

This phase 2, multicenter, double-blind, parallel-group study was conducted at 36 sites in Japan in women with uterine leiomyomas and heavy menstrual bleeding, defined as a pictorial blood loss assessment chart (PBAC) score of ≥ 120 in one menstrual cycle. Patients were randomized 1:1:1:1 to relugolix 10, 20, or 40 mg, or placebo, orally once daily for 12 weeks. The primary endpoint was the proportion of patients with a total PBAC score of < 10 from week 6 to 12. A sample size of 50 patients per group was estimated to provide ≥ 95% power, based on the comparison of relugolix 40 mg with placebo using a chi-square test with a significance level of 5% (two-sided).

RESULTS:

From November 2011 to September 2012, 216 patients were randomized and 214 patients (99.1%) were analyzed. The proportion (difference vs. placebo) of patients that achieved the primary endpoint in the placebo and 10-, 20-, and 40-mg relugolix groups were 0%, 20.8% (95% confidence interval [CI]: 9.3-32.3, P < .001), 42.6% (95% CI: 29.4-55.8, P < .001), and 83.3% (95% CI: 73.4-93.3, P < .001), respectively. Though treatment-emergent adverse events were similar between the 20- and 40-mg groups, the incidence rates were more frequent compared with the placebo group. Most of these adverse events were mild or moderate in intensity.

CONCLUSIONS:

Relugolix decreased menstrual blood loss in women with uterine leiomyomas in a dose-response manner, and was generally well tolerated.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, https://clinicaltrials.gov/ct2/show/NCT01452659 , NCT01452659 (registered 17/10/2011); JAPIC Clinical Trial Information, https://www.clinicaltrials.jp , JapicCTI-111590 (registered 31/08/2011).

• Authors: Hiroshi Hoshiai, Yoshifumi Seki, Takeru Kusumoto, Kentarou Kudou, Masataka Tanimoto
• Journal: BMC women's health (BMC Womens Health) Vol. 21 Issue 1 Pg. 375 (10 28 2021) ISSN: 1472-6874 [Electronic] England
• PMID: 34711224 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Phenylurea Compounds
• Pyrimidinones
• relugolix

Topics

• Female
• Humans
• Leiomyoma (drug therapy)
• Menorrhagia (drug therapy)
• Phenylurea Compounds
• Pyrimidinones
• Treatment Outcome
• Uterine Neoplasms (drug therapy)