CORAL Trial Results on Nalbuphine ER for IPF-Associated Chronic Cough

In the phase 2b randomized, double-blind, placebo-controlled CORAL trial, investigators evaluated nalbuphine extended release (ER) for idiopathic pulmonary fibrosis (IPF)-associated chronic cough and reported greater relative decreases from baseline in objectively measured 24-hour cough frequency at week 6 with nalbuphine ER (47.9%–60.2%) than with placebo (16.9%).

The multicenter trial was conducted at 52 sites across 10 countries with 1:1:1:1 randomization to nalbuphine ER 27 mg twice daily, 54 mg twice daily, 108 mg twice daily, or placebo twice daily for 6 weeks. The primary outcome was the relative change from baseline in 24-hour cough frequency (coughs per hour) measured with a digital cough monitor at week 6. Mean relative decreases in objective cough count at week 6 were reported as 47.9% (P = .008) with 27 mg, 53.4% (P < .001) with 54 mg, and 60.2% (P < .001) with 108 mg, compared with 16.9% with placebo. In the primary analysis, all three nalbuphine ER dose groups were reported to outperform placebo on the digital cough-count endpoint.

Participants had IPF with chronic cough lasting at least 8 weeks and a Cough Severity Numerical Rating Scale score of 4 or higher, reflecting a symptomatic baseline population. The report lists a baseline mean cough count of 28.3 coughs per hour. A key secondary patient-reported outcome was the relative change from baseline at week 6 on the Evaluating Respiratory Symptoms in IPF cough-frequency subscale (lower scores indicating less frequent cough). At week 6, the two higher nalbuphine ER doses were reported to have statistically significant relative improvements vs placebo on this subscale (−40.6%, P = .004, with 54 mg; −40.2%, P < .005, with 108 mg).

Key Takeaways:

• In CORAL, nalbuphine ER dose groups were reported to show larger 6-week reductions in digitally measured 24-hour cough frequency than placebo.
• At week 6, statistically significant improvements on a patient-reported cough-frequency subscale were reported for the 54 mg and 108 mg twice-daily groups vs placebo.