Gefapixant in two randomised dose-escalation studies in chronic cough

Area of Science:

• Pharmacology
• Respiratory Medicine
• Clinical Trials

Background:

• Refractory chronic cough (RCC) poses a significant clinical challenge.
• Gefapixant, a P2X3 receptor antagonist, has shown efficacy in RCC at high doses.
• The current study investigates lower, escalated doses of gefapixant for RCC.

Purpose of the Study:

• To evaluate the efficacy and tolerability of escalating doses of gefapixant in patients with RCC.
• To determine the optimal dose range for gefapixant's anti-tussive effects.
• To assess the dose-response relationship for both efficacy and adverse events.

Main Methods:

• Two randomized, double-blind, placebo-controlled, crossover, dose-escalation studies were conducted.
• Participants received ascending doses of gefapixant (7.5-200 mg) or placebo for 16 days.
• Primary endpoint: awake cough frequency assessed by 24-h ambulatory cough monitoring; secondary endpoints: patient-reported cough severity.

Main Results:

• Gefapixant doses of 30 mg and higher demonstrated statistically significant improvements in cough frequency compared to placebo (p<0.05).
• Similar dose levels showed improvements in patient-reported cough severity.
• Taste disturbance was dose-dependent, with maximal effects observed at doses ≥150 mg.

Conclusions:

• P2X3 antagonism with gefapixant exhibits anti-tussive efficacy.
• Improved tolerability was observed at lower doses than previously investigated.
• Further studies of longer duration are warranted to confirm long-term efficacy and safety.