Gefapixant in two randomised dose-escalation studies in chronic cough.

Abstract

BACKGROUND AND OBJECTIVES:

Gefapixant has previously demonstrated efficacy in the treatment of refractory chronic cough at a high daily dose. 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 end-point 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 and the cough severity diary.

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. Studies of longer duration are warranted.

• Authors: Jaclyn A Smith, Michael M Kitt, Peter Butera, Steven A Smith, Yuping Li, Zhi Jin Xu, Kimberley Holt, Shilpi Sen, Mandel R Sher, Anthony P Ford
• Journal: The European respiratory journal (Eur Respir J) Vol. 55 Issue 3 (03 2020) ISSN: 1399-3003 [Electronic] England
• PMID: 31949115 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright ©ERS 2020.

Chemical References

• Pyrimidines
• Sulfonamides
• Gefapixant

Topics

• Chronic Disease
• Cough (drug therapy)
• Double-Blind Method
• Humans
• Pyrimidines
• Sulfonamides
• Treatment Outcome