Relationship between health-related quality of life and objective cough frequency in a phase 2b trial of gefapixant

Objectives: We evaluated the impact of refractory or unexplained chronic cough (RCC/UCC) frequency on health-related quality of life (HRQoL). Methods: A Phase 2b, 12-week, double-blind RCT included RCC/UCC subjects (cough duration ≥1 year; baseline VAS ≥40 mm) (NCT02612610). Treatment groups (placebo, gefapixant 7.5mg, 20mg, and 50mg) were pooled for this analysis. A sound-recording device (VitaloJAKTM, Vitalograph, Ltd.) was used to assess Awake Cough Frequency (aCF). The Leicester Cough Questionnaire (LCQ; Total, Physical, Psychological and Social scores) assessed HRQoL. Mean baseline LCQ scores across tertiles of aCF (0-33 [lowest], 34-66, and 67-100th percentiles) and baseline to Week 4 changes across aCF responder groups (≥30% reduction vs 1.5, >0.5, and >0.6 on the Total, Physical, Psychological/Social domains are considered meaningful. Results: LCQ and aCF were completed by 251 subjects. At baseline, mean (SE) Total LCQ scores were highest (better) for the lowest tertile of aCF: 13.1 (0.31), 11.2 (0.31), and 10.7 (0.31) for the 0-33, 34-66, and 67-100 percentiles, respectively. A similar trend was observed for the baseline LCQ domain scores. After 4 weeks of treatment, aCF responders had an LS mean (SE) LCQ Total score increase of 4.2 (0.25) while non-responders had an increase of 1.2 (0.28) (p Conclusion: RCC/UCC subjects with higher aCF report worse HRQoL. Clinically meaningful improvements in aCF result in improvements in HRQoL that are consistent with LCQ meaningful change thresholds.