Introduction: In the phase 2a crossover trial (CANAL; NCT04030026), patients with idiopathic pulmonary fibrosis who were treated with oral nalbuphine extended-release tablets had a significant reduction in cough frequency compared with those given placebo. Improvement was also seen in patient-reported outcomes (PROs) of cough. Here we examined the correlation between the change in 24-hr cough count (CC) and change in PROs.

Methods: The 24-hr CC was derived from 24-hr cough frequency data from a digital cough monitor (VitaloJAK) at baseline and day 21 (end of treatment) in the CANAL trial. EXACT is a 14-item electronic diary, of which 11 items measure patient-reported severity of respiratory systems. EXACT 2 (item 2) captures cough frequency on a scale of 0-4 (0=not at all to 4=almost constantly). Cough Severity Numerical Rating Scale (CS-NRS) is a self-assessment of cough severity reported on an 11-point Likert Scale (1=no cough to 10=worst possible cough). Using repeated measures within-patient analysis, the correlation between change in 24-hr CC and change in EXACT 2 and CS-NRS was estimated.

Results: At end of treatment (n=38), the correlation between change from baseline in 24-hr CC and EXACT 2 was 0.3119 (P?0.0001) and between 24-hr CC and CS-NRS was 0.4531 (P=0.0066). The probability of a true positive correlation for EXACT 2 and CS-NRS versus 24-hr CC was estimated to be 99.62%.

Conclusion: Reduction in objective measures of cough is associated with perceived improvements as reflected by cough PROs, EXACT 2 and CS-NRS.

Funding source: Trevi Therapeutics