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

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

Citation

Morice, A. H., Kitt, M. M., Ford, A. P., Tershakovec, A. M., Wu, W. C., Brindle, K., Thompson, R., Thackray-Nocera, S., & Wright, C. (2019). The effect of gefapixant, a P2X3 antagonist, on cough reflex sensitivity: A randomised placebo-controlled study. European respiratory journal, 54(1), Article 1900439. https://doi.org/10.1183/13993003.00439-2019

• Journal Article Type: Article
• Acceptance Date: Apr 3, 2019
• Online Publication Date: Jul 4, 2019
• Publication Date: Jul 4, 2019
• Deposit Date: May 23, 2019
• Publicly Available Date: Jul 5, 2020
• 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
• DOI: https://doi.org/10.1183/13993003.00439-2019
• Keywords: Pulmonary and Respiratory Medicine
• Public URL: https://hull-repository.worktribe.com/output/1835195
• Publisher URL: https://erj.ersjournals.com/content/54/1/1900439
• Contract Date: May 23, 2019