S28 Benefits observed with patient-reported outcomes in a phase 2b clinical trial of gefapixant, a P2X3 receptor antagonist, in chronic cough

Background

The negative impact of chronic cough on patients' daily lives is multi-faceted; therefore, the evaluation of chronic cough treatment requires an approach including both objective and subjective measures. We assessed patient-reported outcomes (PROs) in a phase 2b clinical trial of gefapixant in patients with refractory or unexplained chronic cough (RCC or UCC).

Methods

This Phase 2b, 12-week, randomized controlled trial included subjects with severe RCC or UCC (duration >1 year; baseline VAS≥40 mm). Treatments included placebo or gefapixant (7.5, 20, or 50 mg BID) in a 1:1:1:1 ratio. Awake Objective Cough Frequency at 12 weeks was the primary endpoint; PROs included as secondary endpoints were: Cough Severity Visual Analog Scale (VAS), Patient Global Impression of Change (PGIC), Cough Severity Diary (CSD), and the Leicester Cough Questionnaire (LCQ). VAS is a patient rating of cough severity on a 0–100 mm visual analog scale (no cough to worst cough severity). PGIC is a patient rating of improvement (from very much, much, or minimally improved to no change or minimally, much, and very much worse). CSD was scored daily and summarized weekly and is comprised of 7 items (0–10 [best-worst] scale) including subscales capturing subjects' impression of frequency, disruption, and intensity. LCQ is a 19-item questionnaire (0–7 [worst-best] scale) including domains quantifying patients' impression of physical, psychological and social effects of cough.

Results

253 subjects were randomized with subjects on gefapixant 50 mg demonstrating significant reduction (p<0.01) of Awake Cough Frequency at 12 weeks vs. placebo (Smith et al, Am J Respir Crit Care Med 2017: 195:A7608). Week 12 results for PROs are presented in the table 1. Gefapixant 50 mg demonstrated significantly greater improvement vs. placebo for each PRO with all doses demonstrating significantly greater improvement for PGIC.

Conclusions

Improvements in PROs in this trial are consistent with data on objective cough frequency reductions and indicate benefits related to quality of life, particularly with regard to disruption and psychological impact from cough.