Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study

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Authors

  • Alyn Morice
  • Jaclyn A Smith
  • Lorcan McGarvey
  • Surinder S Birring
  • Sean M Parker
  • Thomas Hummel
  • Isabella Gashaw
  • Lueder Fels
  • Stefan Klein
  • Klaus Francke
  • Christian Friedrich

Colleges, School and Institutes

Abstract

ATP acting via P2X3 receptors is an important mediator of refractory chronic cough (RCC). This phase 2a double-blinded crossover study assessed the safety, tolerability and efficacy of eliapixant (BAY 1817080), a selective P2X3 receptor antagonist, in adults with RCC attending specialist centres.
In period A, patients received placebo for 2 weeks then eliapixant 10 mg for 1 week. In period B, patients received eliapixant 50, 200 and 750 mg twice daily for 1 week per dose level. Patients were randomised 1:1 to period A─B (n=20) or B─A (n=20). The primary efficacy endpoint was change in cough frequency assessed over 24 h (VitaloJAK). Primary safety endpoint was frequency and severity of adverse events (AEs).
Thirty-seven patients completed randomised therapy. Mean cough frequency fell by 17.4% versus baseline with placebo. Eliapixant reduced cough frequency at doses ≥50 mg (reduction versus placebo at 750 mg, 25%: 90% confidence interval, 11.5–36.5%; p=0.002). Doses ≥50 mg also significantly reduced cough severity. AEs, mostly mild or moderate, were reported in 65% of patients with placebo and 41─49% receiving eliapixant. Cumulative rates of taste-related AEs were 3% with placebo and 5−21% with eliapixant: all were mild.
Selective P2X3 antagonism with eliapixant significantly reduced cough frequency and severity, confirming this as a viable therapeutic pathway for RCC. Taste-related side-effects were lower at therapeutic doses than with the less selective P2X3 antagonist gefapixant. Selective P2X3 antagonism appears to be a novel therapeutic approach for RCC.

ClinicalTrials.gov: NCT03310645
Funding: Bayer AG.

Details

Original languageEnglish
JournalThe European respiratory journal
Publication statusAccepted/In press - 6 Apr 2021