A phase 3b, randomized controlled trial of gefapixant in recent-onset chronic cough

Abstract

Objective: Gefapixant improved cough-specific quality of life (QOL) in participants with refractory or unexplained chronic cough (RCC or UCC) and a chronic cough duration ≥1 year in phase 3 studies (McGarvey, L. et al. Lancet 2022; 399:909-923). This study assessed gefapixant in recent-onset RCC or UCC.

Methods: Adults with RCC or UCC, chronic cough (ie, cough duration >8 weeks) for <12 months before screening (ie, cough lasting <14 months), and a ≥40-mm score on a 100-mm cough severity visual analog scale were randomized 1:1 to receive gefapixant 45 mg twice daily (BID) or placebo for 12 weeks. Primary endpoint was change from baseline to Week 12 in Leicester Cough Questionnaire (LCQ) total score (range, 3-21), analyzed using longitudinal analysis of covariance. A post hoc analysis compared proportion of LCQ responders (ie, ≥1.3-point increase from baseline to Week 12 in LCQ total score) between groups.

Results: Of 415 randomized and treated participants, 65% were female and mean (SD) chronic cough duration was 7.2 (2.7) months. Model-based mean change from baseline (95% CI) in LCQ total score at Week 12 was 4.34 (3.84-4.83) for gefapixant and 3.59 (3.09-4.09) for placebo (estimated treatment difference [95% CI]: 0.75 [0.06-1.44]; P=0.034). More participants in the gefapixant vs placebo group were LCQ responders at Week 12 (81% vs 67%; estimated odds ratio [95% CI]: 2.01 [1.21-3.32]). The most common adverse events (AEs) in the gefapixant group were taste related (54%). Incidence of serious AEs was low (<2%) and comparable between groups.

Conclusions: Gefapixant 45 mg BID significantly improved cough-specific QOL vs placebo in recent-onset RCC or UCC, with a similar safety profile to prior studies.