Philip Molyneaux, MD, PhD, a Professor of Interstitial Lung Disease (ILD) at Imperial College London and the Asthma+Lung UK Chair of Respiratory Research at Royal Brompton Hospital, where is also the Director of the UK National Institute for Health and Care Research (NIHR) Clinical Research Facility, discusses the results of the CORAL study.
Dr. Molyneaux, chief investigator of the CORAL phase 2b study, presented the results at CHEST 2025, held October 18-21, 2025 in Phoenix. He reported that up to 80% of patients with ILD have frequent, chronic cough. In CORAL, a randomized, double-blind, parallel-group study of 165 patients with idiopathic pulmonary fibrosis (the most common form of ILD) and a history of chronic cough, nalbuphine extended-release tablets were tested against placebo in reducing 24-hour cough frequency. All patients had a cough severity score of ≥ 4 on the Cough Severity Numerical Rating Scale at baseline.
Patients were randomly assigned to receive placebo or nalbuphine in one of three doses: 27-mg, 54-mg, or 108-mg tablets bid. The primary endpoint of the study was reduction in cough frequency at 6 weeks, measured via a digital cough monitor. Secondary endpoints included safety, and changes in several patient-reported questionnaires and scoring indexes.
All doses produced statistically significant decreases in 24-hour cough frequency, but the higher doses produced greater reductions from baseline at 6 weeks compared with placebo (placebo, –17%; nalbuphine 27 mg, –48% [P < .05]; nalbuphine 54 mg, –53% [P < .001]; nalbuphine 108 mg, –60% [P < .001]). Furthermore, a reduction in cough was seen by week 2.
For patients receiving active therapy, the most common adverse events were nausea, vomiting, constipation, and dizziness. There was no difference in discontinuation rates in patients receiving placebo or any nalbuphine doses.
Dr. Molyneaux stated that not only did objectively measured cough frequency decrease, but patients also gained additional benefits within 2 weeks of taking nalbuphine, as determined by patient-reported outcomes data.