Nalbuphine ER Tablets Show Promise as Cough Therapy in Patients with IPF

Toby Maher, MD, PhD

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In a recent crossover trial, patients with idiopathic pulmonary fibrosis (IPF) showed reduced cough after treatment with nalbuphine extended-release tablets (NAL ER). The investigators, led by Toby Maher, MD, PhD, Keck School of Medicine, University of Southern California, stated there are currently no cough therapies approved for this population.¹

Because IPF is a progressive lung disease that scars the lung tissue, the lung function of these patients is compromised and accompanied by respiratory symptoms, cough is one of the most common.

NAL ER Dosage

The study was a randomized, double-blind, placebo-controlled crossover trial that involved a pair of 22-day treatment periods, with a 2-week washout period in between. NAL ER was administered at an initial dose of 27 mg once daily, which was then titrated up to 162 mg twice daily by day 16.

Investigators assessed the percent change from baseline in hourly daytime objective cough frequency, as measured by an electronic cough monitor, for the primary endpoint of the study. Changes in objective 24-hour cough frequency, cough severity, and breathlessness, based on patient-reported outcomes were secondary endpoints.

Reducing Cough in Patients with IPF

The analysis included 41 patients with IPF who received at least one dose of study medication after being randomly assigned. During the NAL ER treatment period, the team observed a significant reduction in daytime objective cough frequency, with a 75.1% decrease compared with the placebo treatment period's reduction of 22.6%.

Investigators reported the finding corresponded to a 52.5 percentage point decrease from baseline (P < 0.001) at day 21, when adjusting for placebo effects. The therapy demonstrated a 76.1% decrease (95% CI, 83.1-69.1) in 24-hour objective cough frequency, while the placebo only showed a 25.3% decrease (43.9-6.7), resulting in a 50.8 percentage point placebo-adjusted change.

Balancing Adverse Events

Common adverse events exhibited with the treatment included nausea, fatigue, constipation, and dizziness, which were more frequent compared with the placebo group and should be considered when evaluating the overall benefit-risk profile of NAL ER in this population, investigators said.

“These safety results are similar to those of a trial of low-dose morphine in chronic cough that reported constipation and drowsiness in 40% and 25% of patients, respectively,” the research stated.

Based on the short-term crossover trial results, the team suggested that NAL ER shows promise in reducing cough frequency for individuals with IPF. Given the lack of approved therapies targeting this clinical concern, the findings indicated significant development in the field, according to the study.

However, it was acknowledged that further research is needed to contribute to a better understanding of the treatment's overall efficacy, tolerability, and clinical utility in the management of cough in IPF patients.

Particularly, larger and longer trials evaluating the long-term efficacy and safety of the treatment as a cough therapy. Additionally, the impact of the treatment on cough severity and patient-reported outcomes should also be further explored.

“Although our trial was not designed to statistically test other outcomes, the data are encouraging enough to merit further assessment in longer and larger clinical studies. Such trials permit weighing the long-term effects on cough against the adverse effects and loss of efficacy due to habituation associated with chronic opiate use,” investigators wrote.

References:

1. Maher TM, Avram C, Bortey E, et al. Nalbuphine Tablets for Cough in Patients with Idiopathic Pulmonary Fibrosis. NEJM Evidence. 2023