Abstract
Background Gefapixant has previously demonstrated efficacy in the treatment refractory chronic cough at a high, daily dose.
Objectives The current investigations explore efficacy and tolerability of gefapixant, a P2X3 receptor antagonist, for the treatment of chronic cough using a dose escalation approach.
Materials and methods Two randomised, double-blind, placebo-controlled, crossover, dose-escalation studies recruited participants with refractory chronic cough. Patients were assigned to receive ascending doses of gefapixant (study 1: 50–200 mg, study 2: 7.5–50 mg) or placebo for 16 days, then crossed-over after washout. The primary endpoint was awake cough frequency assessed using a 24 h ambulatory cough monitor at baseline and on day 4 of each dose. Patient reported outcomes included a cough severity visual analogue scale (VAS) and Cough Severity Diary (CSD).
Results In clinical studies, gefapixant doses ≥30 mg produced maximal improvements in cough frequency compared with placebo (p<0.05); reported cough severity measures improved at similar doses. Taste disturbance exhibited a different relationship with dose, apparently maximal at doses ≥150 mg.
Conclusions P2X3 antagonism with gefapixant demonstrates anti-tussive efficacy and improved tolerability at lower doses than previously investigated. Longer duration studies are warranted.
Footnotes
This 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 Smith reports grants and personal fees from Merck Inc, during the conduct of the study; grants and personal fees from Glaxosmithkline, grants and personal fees from NeRRe Pharmaceuticals, grants and personal fees from Menlo, grants and personal fees from Bayer, personal fees from Boehringer Ingleheim, personal fees from Genentech, personal fees from Neomed, non-financial support from Vitalograph, personal fees from Cheisi, grants and personal fees from Afferent, personal fees from Bellus, grants and personal fees from Axalbion, personal fees from AstraZeneca, outside the submitted work; In addition, Dr Smith has a patent A method for generating output data licensed.
Conflict of interest: Dr Kitt reports other from Merck/Afferent, during the conduct of the study; other from Merck/Afferent, outside the submitted work.
Conflict of interest: Dr Butera reports other from Afferent Pharmaceuticals, Inc., during the conduct of the study; other from Afferent Pharmaceuticals, Inc., outside the submitted work; and I was an employee of Afferent Pharmaceuticals, Inc..
Conflict of interest: Mr. Smith reports personal fees from Afferent Pharmaceuticals, during the conduct of the study
Conflict of interest: Dr Li reports personal fees from Afferent/Merck & Co., Inc, during the conduct of the study.
Conflict of interest: Dr Xu has nothing to disclose.
Conflict of interest: Ms. Holt has nothing to disclose.
Conflict of interest: Dr Sen has nothing to disclose.
Conflict of interest: Dr sher reports personal fees from Afferent, personal fees from Merck, during the conduct of the study; and Consultant to Bellus, Bayer, NeRRe with clinical studies with Menlo and NeRRe.
Conflict of interest: Dr Ford has nothing to disclose.
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- Received August 13, 2019.
- Accepted December 19, 2019.
- Copyright ©ERS 2020
