The Efficacy and Safety of Gefapixant in a Phase 3b Trial of Patients with Recent-Onset Chronic Cough

Abstract

Purpose: We evaluated gefapixant, a P2X3 receptor antagonist, in participants with recent-onset (≤ 12 months) refractory chronic cough (RCC) or unexplained chronic cough (UCC).

Methods: Participants (≥ 18 years of age; ≥ 40 mm on a 100-mm cough severity visual analog scale [VAS] at screening and randomization) with chronic cough for < 12 months were enrolled in this phase 3b, double-blind, placebo-controlled, parallel group, multicenter study (NCT04193202). Participants were randomized 1:1 to gefapixant 45 mg BID or placebo for 12 weeks with a 2-week follow-up. The primary efficacy endpoint was change from baseline at Week 12 in Leicester Cough Questionnaire (LCQ) total score. Adverse events were monitored and evaluated.

Results: There were 415 participants randomized and treated (mean age 52.5 years; median [range] duration 7.5 [1-12] months): 209 received placebo and 206 received gefapixant 45 mg BID. A statistically significant treatment difference of 0.75 (95% CI: 0.06, 1.44; p = 0.034) for gefapixant vs. placebo was observed for change from baseline in LCQ total score at Week 12. The most common AE was dysgeusia (32% gefapixant vs. 3% placebo participants); serious AEs were rare (1.5% gefapixant vs. 1.9% placebo participants).

Conclusion: Gefapixant 45 mg BID demonstrated significantly greater improvement in cough-specific health status from baseline compared to placebo, in participants with recent-onset chronic cough. The most common AEs were related to taste and serious AEs were rare.

Keywords: Antitussives; Chronic cough; P2X3 receptor antagonists; Refractory chronic cough; Unexplained chronic cough.

Conflict of interest statement

LPM has received grants and personal fees from Merck Sharp & Dohme; personal fees from Applied Clinical Intelligence; grants from Asthma UK, Northern Ireland Chest Heart and Stroke, NC3Rs, British Heart Foundation, and Chiesi; travel and subsistence for attendance at scientific meetings from Boehringer Ingelheim, GlaxoSmithKline, and Chiesi; and advisory board or consultancy fees from Almirall, NAPP, GlaxoSmithKline, and Boehringer Ingelheim. MRS has received grants and personal fees from Merck & Co., Inc; is a consultant to Bayer, Bellus, and NeRRe Therapeutics; and has done clinical research with Bellus. YGS reports no conflicts. SL, WCW, PX, JS, CL, AMN, PAR, and ASA are current or former employees of Merck & Co., Inc., Rahway, NJ, USA.

© 2023. The Author(s).

Figures

Fig. 1

Study design

Fig. 2

CONSORT diagram

Fig. 3

LS mean change from baseline in efficacy endpoints over 12 Weeks