Late Breaking Abstract - Two Phase 3 Randomized Clinical Trials of Gefapixant, a P2X3 Receptor Antagonist, in Refractory or Unexplained Chronic Cough (COUGH-1 and COUGH-2)
Lorcan McGarvey, Surinder S. Birring, Alyn H. Morice, Peter V. Dicpinigaitis, Ian Pavord, Jonathan Schelfhout, Allison Martin Nguyen, Qing Li, Anjela Tzontcheva, Beata Iskold, Stuart Green, Carmen La Rosa, David Muccino, John A. Smith
Abstract
<b>Background:</b> COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are double-blind, randomized placebo-controlled, Phase 3 trials of gefapixant, a P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). <b>Methods:</b> Participants were ≥18 yrs, had chronic cough ≥ 1 yr, an RCC/UCC diagnosis, and a screening and baseline cough severity VAS score ≥40 mm; they were randomized to placebo (pbo), gefapixant 15 mg BID, or gefapixant 45 mg BID. Primary endpoints were 24h cough frequency at 12 Wks (COUGH-1) and 24 Wks (COUGH-2) (analyzed with longitudinal ANCOVA based on log-transformed data). <b>Results:</b> A total of 2,044 participants (75% female, mean age 58 yrs, mean cough duration 11 yrs) were randomized/treated in COUGH-1 (n=730) and COUGH-2 (n=1314). Despite a larger-than-anticipated pbo response, gefapixant 45 mg demonstrated significant reduction in 24h cough frequency vs. pbo in both trials. The 15 mg dose failed to demonstrate a reduction in cough frequency vs. pbo. Overall adverse events (AE) and taste-related AEs occurred at higher incidence with 45 mg vs. pbo or 15 mg; serious-AE incidence was similar between treatments (Table). <b>Conclusions:</b> Treatment with gefapixant 45 mg BID resulted in significant reduction in 24h cough frequency in participants with RCC/UCC. Serious AEs were infrequent and AEs with gefapixant 45 mg were most commonly related to taste.