Nalbuphine ER Improves Chronic Cough in idiopathic pulmonary fibrosis: Study

A new study published in the Journal of the American Medical Association showed that all three doses of extended-release nalbuphine effectively decreased the objective frequency of coughing in patients with chronic cough associated with idiopathic pulmonary fibrosis (IPF).

IPF patients' quality of life is negatively impacted by cough. And so, better therapies for IPF-associated cough are required. To ascertain if nalbuphine extended release (ER), a k-opioid receptor agonist and μ-opioid receptor antagonist, reduces cough in patients with IPF-associated cough when compared to a placebo, this study was carried out.

The patients with IPF who had a persistent cough for at least 8 weeks and a score of four or higher on the Cough Severity Numerical Rating Scale (0, no cough; 10, worst possible cough) were enrolled in this trial at 52 sites across ten countries between February 2024 and February 2025.

For six weeks, patients were randomized 1:1:1:1 to receive either a placebo or nalbuphine ER twice daily at dosages of 27 mg, 54 mg, or 108 mg. The main result was the relative difference between nalbuphine ER and placebo at week six in terms of 24-hour cough frequency (coughs/h), as determined by a digital cough monitor. The patient-reported cough frequency (Evaluating Respiratory Symptoms in IPF cough subscale; scores range from 0-4, lower scores imply decreased cough frequency) at week six was the primary secondary outcome.

Of the 223 patients who were screened, 160 were taken into account in the primary analysis (median age, 71 [range, 51-85] years; 28.5% female) and 165 were randomized (42, 43, 40, and 40 to receive nalbuphine ER 27 mg, 54 mg, and 108 mg, and placebo, respectively). 28.3 (27.4) coughs per hour was the baseline mean (SD) cough count.

In comparison to the placebo group (16.9%; from 29.4 to 28.1 coughs/h), the mean relative reduction in the cough count and the absolute decrease in coughs/h were 47.9% (from 24.6 to 11.9; P =.008), 53.4% (from 28.0 to 14.9; P <.001), and 60.2% (from 31.5 to 11.9; P <.001).

In the 27-mg, 54-mg, and 108-mg groups, the relative and absolute changes for the primary secondary outcome of patient-reported cough frequency at week 6 were −31.4% (from 2.3 to 1.5; P =.14), −40.6% (from 2.6 to 1.4; P =.004), and −40.2% (from 2.4 to 1.4; P <.005). Overall, the objectively measured cough frequency was reduced in all three doses of extended-release nalbuphine in patients with IPF-related chronic cough.

Source:

Molyneaux, P. L., Mogulkoc, N., Gunen, H., Doboszynska, A., Kreuter, M., Neustifter, B., Mathur, V., Cassella, J., & CORAL Study Group. (2026). Oral nalbuphine in idiopathic pulmonary fibrosis-associated cough: The CORAL randomized clinical trial. The Journal of the American Medical Association. https://doi.org/10.1001/jama.2025.26179