B95-02 A Phase 2b Trial (CORAL) of Nalbuphine Extended-release Tablets in Patients With Idiopathic Pulmonary Fibrosis Experiencing Chronic Cough: Primary and Subgroup Analyses
Makaleler > Tam Makale · 2026
Yazarlar: P L Molyneaux, N Mogulkoc Bishop, H Gunen, A Doboszyńzska, M Kreuter, V Mathur, J Cassella, CORAL Study Group
American Journal of Respiratory and Critical Care Medicine, Uluslararası, Wos, 2026, cilt 212
DOI: 10.1093/ajrccm/aamag162.2616
Özet
Abstract Rationale More than 80% of patients with idiopathic pulmonary fibrosis (IPF) experience chronic cough (CC). Although antifibrotics are used to treat IPF, there are no approved therapies targeting cough in this population. Nalbuphine extended-release (NAL ER) is a kappa opioid receptor agonist and mu opioid receptor antagonist that acts centrally and peripherally on the cough reflex arc. In the CORAL trial (NCT05964335), we evaluated the efficacy and safety of NAL ER tablets in patients with IPF-associated CC. Methods CORAL was a randomized, double-blind, placebo (PBO)-controlled study of 165 patients with IPF and a history of CC (≥8 weeks) assigned 1:1:1:1 to receive NAL ER (27, 54, or 108 mg twice daily [BID]) or PBO BID for 6 weeks. The primary end point was relative change from baseline in 24-hour objective cough frequency (coughs/h) at Week 6. Subgroup analyses of the primary end point were conducted post hoc, based on background antifibrotic use and baseline cough frequency, by repeating the primary endpoint mixed model for repeated measures within subgroups. Results Treatment with NAL ER significantly reduced 24-hour objective cough frequency at Week 6 (primary endpoint); the PBO-adjusted relative change from baseline was −30.9% (P<.01), −36.5% (P<.001), and −43.3% (P<.001) in the 27-mg, 54-mg, and 108-mg BID groups, respectively. The findings within subgroups were generally consistent with those of the overall study population. Comparisons to PBO with nominal p-values were: background antifibrotics (N = 117; 27 mg, P<.05; 54 mg, P<0.001; 108 mg, P<.01); no antifibrotics (N = 34; 27 mg, P<.05; 54 mg, P<.05; 108 mg, P<.001); baseline cough count ≤10 coughs/h (N = 34; 54 mg, P<.05; 108 mg, P<.05); and baseline cough count >10 coughs/h (N = 117; 54 mg, P<.001; 108 mg, P<.001). In prespecified responder analyses at Week 6, there was a significant difference in the proportions of patients with ≥50% reduction in objective cough frequency for all dose groups vs PBO. Additionally, 43.2% of patients (P<.01) in the 108 mg BID group and 37.1% (P<.01) in the 54 mg BID group (vs. 5.6% in PBO) achieved a ≥ 75% reduction in 24-hour cough frequency. Discontinuations due to treatment-emergent adverse events (TEAEs) were similar between the combined NAL ER (5.6%) and PBO (5.0%) groups. The 4 most common TEAEs were nausea, vomiting, constipation, and dizziness. Conclusions NAL ER treatment significantly reduced cough frequency in patients with IPF; effects were consistent across subgroups stratified by antifibrotic use and baseline cough count. This abstract is funded by: Trevi Therapeutics