S15 Efficacy of oral nalbuphine extended release for the treatment of chronic cough in idiopathic pulmonary fibrosis: analysis of a phase 2 study

Abstract

<h3>Introduction and Objective</h3> Most patients with idiopathic pulmonary fibrosis (IPF) are affected by chronic cough causing physical, emotional, and psychological stress. Cough has also been hypothesised as potential driver of the underlying fibrotic process. Currently, no effective treatment for cough in IPF exists. Mixed opioid agonists/antagonists may reduce chronic cough by pharmacologically acting on the opioid system at both the peripheral and central nervous system level. We report the interim analysis of a phase 2 study of an extended-release (ER) oral formulation of the dual-acting κ-opioid receptor agonist/µ-opioid receptor antagonist nalbuphine (NAL) for IPF-related chronic cough (NCT04030026). <h3>Methods</h3> The study was a randomised, double-blind, placebo-controlled crossover trial comprising two 22-day treatment periods (Period 1: NAL ER-placebo; Period 2: placebo-NAL ER) separated by a 2-week washout. Adult patients diagnosed with IPF and chronic cough (duration &gt;8 weeks) were enrolled. Eligible patients were randomised to either NAL ER or placebo. The starting dose of NAL ER 27 mg once daily was titrated to NAL ER 162 mg twice daily at Day 16. The primary endpoint was the mean percent change from baseline in daytime hourly cough frequency as measured by an objective digital monitor (VitaloJAK®) and analysed with a mixed-effects model. A patient-reported outcome instrument (EXACT2) was used to assess daily cough frequency. <h3>Results</h3> 45 patients were screened, and 32 were enrolled/randomised; the Period 1 full analysis set comprised 26 patients. Patients were primarily male, mean age 72 years, and with daytime cough frequency of 31/hour. Reduction in hourly cough frequency from baseline to Day 22 was 77.3% with NAL ER vs 25.7% for placebo (51.6% placebo-adjusted difference; p&lt;0.0001). Overall, 42% of NAL ER-treated patients (vs’0% for placebo) achieved a 75% reduction in cough frequency (figure 1). Preliminary analysis of EXACT2 shows patient-reported cough frequency to be consistent with VitaloJAK® data, and indicates early improvement with NAL ER vs placebo. No new safety signals related to nalbuphine were identified when compared to previous human clinical trial data. <h3>Conclusions</h3> In this interim analysis of phase 2 data, NAL ER shows a significant reduction in IPF-related hourly daytime chronic cough frequency vs placebo. Please refer to page A208 for declarations of interest related to this abstract.