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

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. Subjects: 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.