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)

Abstract

Background: 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). Methods: 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). Results: 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). Conclusions: 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.