A110-17 The Effect of Nalbuphine Extended Release on Cough Bouts in Patients With Idiopathic Pulmonary Fibrosis From a Phase 2b Randomized Clinical Trial (CORAL)

Abstract Rationale More than 80% of patients with idiopathic pulmonary fibrosis (IPF) experience chronic cough, for which there are no approved therapies. Oral nalbuphine extended release (NAL ER) is a kappa receptor agonist and mu receptor antagonist that acts on the cough reflex arc centrally and peripherally by targeting opioid receptors involved in cough. In a phase 2b trial (CORAL; NCT05964335), patients with IPF treated with NAL ER demonstrated a significant reduction in 24-hour objective cough frequency vs placebo (PBO). Although the primary endpoint was 24-hour cough frequency (coughs/hour) from a digital cough monitor (VitaloJAK), coughs typically cluster into bouts, which may be more impactful for patients. In this post hoc analysis, we examined the effect of NAL ER on cough bouts (ie, clusters of sequential coughs). Methods CORAL was a randomized, double-blind, PBO-controlled study in which 165 patients with IPF and a history of chronic cough (≥8 weeks) were randomly assigned 1:1:1:1 to receive NAL ER (27, 54, or 108 mg twice daily BID) or PBO BID for 6 weeks. Cough bouts were analyzed from 24-hour cough frequency data at baseline and Week 6. Cough bouts (≥2 coughs) were generated by combing consecutive cough sounds within 2 seconds of one another and analyzed using a mixed model repeated measures analysis. Results Cough bout data were analyzed in a total of 164 patients. Mean number of baseline 24-hour cough bouts were 150.4 (PBO), 126.7 (27 mg BID), 162.1 (54 mg BID), and 153.7 (108 mg BID). At Week 6, mean number of 24-hour cough bouts were 132.0 with PBO (N = 36), 61.4 with 27 mg BID (N = 40), 91.0 with 54 mg BID (N = 34), and 61.3 with 108 mg BID (N = 37). Compared with PBO, treatment with NAL ER significantly reduced the number of cough bouts at Week 6 relative to baseline in all dose groups; the relative change from baseline was −13.4% with PBO, −48.9% with 27 mg BID (P=.0007), −44.3% with 54 mg BID (P=.0042), and −56.7% with 108 mg BID (P.0001). Conclusions Consistent with results observed for cough frequency, NAL ER significantly reduced the number of cough bouts compared with PBO in patients with IPF. This abstract is funded by: Trevi Therapeutics