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The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: A randomised placebo-controlled study

Morice, Alyn H.; Kitt, Michael M.; Ford, Anthony P.; Tershakovec, Andrew M.; Wu, Wen-Chi; Brindle, Kayleigh; Thompson, Rachel; Thackray-Nocera, Susannah; Wright, Caroline

Authors

Alyn H. Morice

Michael M. Kitt

Anthony P. Ford

Andrew M. Tershakovec

Wen-Chi Wu

Kayleigh Brindle

Rachel Thompson

Susannah Thackray-Nocera

Caroline Wright



Abstract

We evaluated the effect of gefapixant on cough reflex sensitivity to evoked tussive challenge.

In this phase 2, double-blind, two-period study, patients with chronic cough (CC) and healthy volunteers (HV) were randomised to single-dose gefapixant 100 mg or placebo in a crossover fashion. Sequential inhalational challenges with ATP, citric acid, capsaicin and distilled water were performed 1, 3 and 5 h after dosing. Mean concentrations evoking ≥2 coughs (C2) and ≥5 coughs (C5) post dose versus baseline were co-primary endpoints. Objective cough frequency (coughs·h−1) over 24 h and a cough severity visual analogue scale (VAS) were assessed in CC patients. Adverse events were monitored.

24 CC patients and 12 HV were randomised (mean age 61 and 38 years, respectively). The cough challenge threshold increased for ATP by 4.7-fold (C2, p≤0.001) and 3.7-fold (C5, p=0.007) for gefapixant versus placebo in CC patients; in HV, C2 and C5 increased 2.4-fold (C2, p=0.113; C5, p=0.003). The distilled water C2 and C5 thresholds increased significantly (p

Journal Article Type Article
Publication Date Jul 4, 2019
Journal European respiratory journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 54
Issue 1
Article Number 1900439
APA6 Citation Morice, A. H., Kitt, M. M., Ford, A. P., Tershakovec, A. M., Wu, W., Brindle, K., …Wright, C. (2019). The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: A randomised placebo-controlled study. The European respiratory journal, 54(1), https://doi.org/10.1183/13993003.00439-2019
DOI https://doi.org/10.1183/13993003.00439-2019
Keywords Pulmonary and Respiratory Medicine
Publisher URL https://erj.ersjournals.com/content/54/1/1900439

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