Randomized, controlled, proof-of-concept trial of gefapixant for endometriosis-related pain.

Autor:	Arbelaez F; Merck & Co., Inc., Rahway, New Jersey., Joeng HK; Merck & Co., Inc., Rahway, New Jersey., Hussain A; Merck & Co., Inc., Rahway, New Jersey., Sunga S; Merck & Co., Inc., Rahway, New Jersey., Guan Y; Merck & Co., Inc., Rahway, New Jersey., Chawla A; Merck & Co., Inc., Rahway, New Jersey., Carmona F; Hospital Clínic, University of Barcelona, Barcelona, Spain., Lines C; Merck & Co., Inc., Rahway, New Jersey., Mendizabal G; Merck & Co., Inc., Rahway, New Jersey. Electronic address: geraldine.mendizabal@merck.com.
Jazyk:	angličtina
Zdroj:	Fertility and sterility [Fertil Steril] 2024 Sep 12. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1016/j.fertnstert.2024.09.013
Abstrakt:	Objective: To evaluate the P2X3 receptor antagonist, gefapixant, for treating moderate-to-severe endometriosis-related pain. Design: Randomized, double-blind, phase 2, and proof-of-concept trial. Setting: Outpatients at hospitals, medical centers or clinical research sites. Patient(s): Premenopausal women age 18-49 years with moderate-to-severe endometriosis-related pain who were not using hormonal treatment. Intervention(s): Gefapixant (45-mg twice daily) or placebo over two menstrual cycles. Main Outcome Measure(s): Participants rated peak pelvic pain severity daily on a 0 (no pain) - 10 (extremely severe pain) scale. The primary endpoint was change from baseline in average daily peak pelvic pain severity during treatment cycle 2. Result(s): All 187 participants randomized (gefapixant, N = 94; placebo, N = 93) took ≥1 dose of investigational treatment and all but six in each treatment group completed the trial. The model-based least-squares mean reduction from baseline in average daily peak pelvic pain severity during treatment cycle 2 was -2.2 for gefapixant and -1.7 for placebo (difference, -0.5; 95% confidence interval, -1.01 to 0.03). In secondary analyses, the difference between gefapixant and placebo in peak pelvic pain severity reduction from baseline on menstrual days was -0.6 (95% confidence interval, -1.18 to -0.06) and -0.5 (95% confidence interval, -1.04 to 0.03) on nonmenstrual days. Taste-related adverse events were reported in 31.9% of participants for gefapixant vs. 4.3% for placebo. Pharmacokinetic assessments at months 1 and 2 clinic visits indicated that of the 94 participants in the gefapixant group, 39 had detectable levels of gefapixant in the blood for both assessments although 38 had no detectable levels for ≥1 assessment. Conclusion(s): Gefapixant (45-mg twice daily) was not shown to be superior to placebo in reducing endometriosis-related pain, although the results directionally favored gefapixant. This trial result should be considered inconclusive given possible issues with treatment compliance. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03654326. Competing Interests: Declaration of Interests F.A. is a former employee of, and owned stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. H.-K.J. is a former employee of, and owned stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. A.H. is an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. S.S. is an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. Y.G. is an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. A.C. is an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. F.C. was an investigator in the study. C.L. an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. G.M. is an employee of, and owns stock/stock options in, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, New Jersey. (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu