TY - JOUR T1 - Eliapixant (BAY 1817080), a P2X3 receptor antagonist, in refractory chronic cough: a randomised, placebo-controlled, crossover phase 2a study JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.04240-2020 SP - 2004240 AU - Alyn Morice AU - Jaclyn A. Smith AU - Lorcan McGarvey AU - Surinder S. Birring AU - Sean M. Parker AU - Alice Turner AU - Thomas Hummel AU - Isabella Gashaw AU - Lueder Fels AU - Stefan Klein AU - Klaus Francke AU - Christian Friedrich Y1 - 2021/01/01 UR - http://erj.ersjournals.com/content/early/2021/04/16/13993003.04240-2020.abstract N2 - 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.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr Morice reports grants, personal fees, non-financial support and other from Bayer AG, grants, personal fees, non-financial support and other from Bayer US, during the course of the study; personal fees, non-financial support and other from Bellus Health, personal fees, non-financial support and other from Merck Sharp & Dohme Corp, personal fees and non-financial support from AstraZeneca, grants, personal fees, non-financial support and other from Sanofi, personal fees and non-financial support from Chiesi Ltd, grants, personal fees and non-financial support from GlaxoSmithKline, personal fees and non-financial support from Boehringer Ingelheim, grants, personal fees and other from NeRRe Therapeutics, grants, personal fees and non-financial support from Respivant Sciences, Inc, grants, personal fees and non-financial support from Philips Respironics, grants from Menio Therapeutics, outside the submitted work.Conflict of interest: Dr Smith reports grants and personal fees from Bayer AG, during the course of the study; grants and personal fees from Bellus Health, grants and personal fees from Shionogi Inc, grants and personal fees from Merck Inc, outside the submitted work; and the VitaloJAK algorithm has been licensed by Manchester University NHS Foundation Trust and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). Manchester University NHS Foundation Trust receives royalties which may be shared with the clinical division in which Jaclyn Smith works.Conflict of interest: Dr McGarvey reports grants and personal fees from Bayer AG, during the conduct of the study; grants and personal fees from Merck & Co., Inc., grants, personal fees and non-financial support from Chiesi, grants and personal fees from Bellus Health, non-financial support from Boehringer Ingelheim, personal fees from Applied Clinical Intelligence, personal fees from Shionogi Inc., personal fees from GlaxoSmithKline, personal fees from NeRRe Therapeutics, from Nocion Therapeutics, other from AstraZeneca, outside the submitted work.Conflict of interest: Dr Birring reports personal fees from Bayer, grants and personal fees from Merck, personal fees from Shionogi, personal fees from Bellus Health, personal fees from NeRRe Therapeutics, personal fees from Nocio, personal fees from Boehringer Ingelheim, personal fees from GlaxoSmithKline, outside the submitted work.Conflict of interest: Dr Parker reports personal fees from Menlo, personal fees from Merck, outside the submitted work.Conflict of interest: Dr Turner has nothing to disclose.Conflict of interest: Dr Hummel reports grants from Sony (Stuttgart, Germany), grants from Smell and Taste Lab (Geneva, Switzerland), grants from Takasago (Paris, France), grants from aspuraclip (Berlin, Germany), personal fees from Frequency Therapeutics (Farmington, CT, USA), personal fees from Baiafoods (Madrid, Spain), outside the submitted work.Conflict of interest: Dr Gashaw reports other from Bayer AG, during the conduct of the study.Conflict of interest: Dr Fels reports personal fees from Bayer AG, during the conduct of the study.Conflict of interest: Dr Klein reports personal fees from Bayer AG, during the conduct of the study.Conflict of interest: Dr Franke reports personal fees from Bayer AG, during the conduct of the study.Conflict of interest: Dr Friedrich reports personal fees from Bayer AG, during the conduct of the study. 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