A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 2b Trial of P2X3 Receptor Antagonist Sivopixant for Refractory or Unexplained Chronic Cough

• DOI: 10.1007/s00408-022-00592-5
• Publication Date: 2022-12-13T09:03:05Z
• Authors: Lorcan McGarvey; Jaclyn A. Smith; Alyn Morice; Surinder S. Birring; Kian Fan Chung; Peter V. Dicpinig...; Akio Niimi; Michael S. Benninger; Mandel Sher; Yuko Matsunaga; Sayaka Miyazaki; Mitsuaki Machida; Hiroyuki Ishihara; Adnan Mahmood; Juan-Carlos Gomez
• Keywords: Refractory (planetary science); Clinical endpoint; Chronic Cough

Abstract Introduction To determine the optimal dose of sivopixant, a highly selective P2X3 receptor antagonist, for refractory or unexplained chronic cough (RCC/UCC). Methods In this phase 2b, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, patients received sivopixant 50, 150, 300 mg placebo once daily 4 weeks. The primary endpoint was change from baseline in 24-h frequency (coughs/h) with vs placebo. Results Overall, 390/406 randomized completed study. Placebo-adjusted changes hourly count over 24 h were 13.17% ( P = 0.3532), − 1.77% 0.8935), and 12.47% 0.3241) severity (visual analog scale) 1.75 mm 0.5854), 1.21 0.7056), 6.55 0.0433) mg, respectively. Leicester Cough Questionnaire total scores 0.37 0.4207), 0.07 0.8806), 0.69 0.1473) Additionally, 61.3%, 78.3%, 86.8%, 71.4% receiving placebo, respectively, reported any improvements Patient Global Impression Change. incidence treatment-emergent adverse events (TEAEs) 25.7%, 32.0%, 49.0%, 20.6% groups, respectively; all TEAEs group mild-to-moderate. Conclusion Sivopixant did not demonstrate statistically significant difference frequency. has potential RCC/UCC, showing greatest patient-reported outcomes dose-related mild to moderate reversible taste disturbance, although further trials are needed. Clinical Trial Registration ClinicalTrials.gov identifier NCT04110054; registered September 26, 2019.