Late Breaking Abstract - Responder analysis of nalbuphine extended-release in refractory chronic cough: results from the RIVER phase 2a trial

<bold>Background:</bold> Nalbuphine extended-release (NAL ER) acts on the cough reflex arc both centrally and peripherally as a kappa agonist and a mu antagonist (KAMA), targeting opioid receptors involved in controlling chronic cough. <bold>Aims and Objectives:</bold> The RIVER (<ext-link>NCT05962151</ext-link>) trial evaluated NAL ER for the treatment of refractory chronic cough (RCC). <bold>Methods:</bold> This double-blind, randomized, placebo (PBO)-controlled, crossover study enrolled and stratified patients with RCC into 2 subgroups based on 24-hour objective cough frequency at screening: moderate (10-19 coughs/h) and severe (≥20 coughs/h). Patients were randomly assigned to one of two 21-day treatment sequences: NAL ER to placebo or placebo to NAL ER, with a 21-day washout between treatments. NAL ER dose was titrated every 7 days (27 mg, 54 mg, and 108 mg, all twice daily [BID]). <bold>Results:</bold> Sixty-six patients were randomized. Clinically meaningful improvements in 24-hour cough frequency (≥30% reduction) were seen in 87% of patients treated with NAL ER (day 21, 108 mg BID). At higher thresholds, NAL ER treatment also had significantly more responders than PBO (all P<.0001; Figure); more than half of patients (54%) achieved a 75% reduction in cough frequency after receiving NAL ER 108 mg BID. No serious treatment-emergent adverse events were reported. <bold>Conclusions:</bold> These results support further investigation of NAL ER for the treatment of RCC. <fig><object-id>erj;66/suppl_69/PA2059/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>