Jacky Smith, MB, ChB, FRCP, PhD, Chair of Respiratory Medicine at the University of Manchester, discusses topline results from the phase 2a RIVER trial for patients with refractory chronic cough (RCC).
Topline results and a responder analysis from the RIVER clinical trial were presented at the 2025 European Respiratory Society conference. This study was a phase 2a, double-blind, placebo-controlled, crossover study of nalbuphine ER versus placebo in patients with RCC. The trial enrolled 66 patients with RCC stratified by 24-hour cough frequency at screening (10-19 coughs per hour and 20 or more coughs per hour).
Patients were randomly assigned to 1 of 2 21-day treatment sequences: nalbuphine ER to placebo or placebo to nalbuphine ER, with a 21-day washout between treatment. Nalbuphine ER was titrated every 7 days from 27 mg twice daily to 108 mg twice daily. The primary endpoint was relative change from baseline in 24-hour objective cough frequency at day 21 in all patients measured by an objective digital cough monitor.
Results illustrated that at day 21, there was a 56% placebo-adjusted reduction in cough frequency with nalbuphine ER 108 mg. The responder analysis showed that 87% of patients achieved a 30% or greater reduction in 24-hour cough frequency with nalbuphine ER 108 mg at day 21, which is considered a clinically meaningful improvement. More than half of patients achieved a 75% reduction in cough frequency at day 21 with nalbuphine ER 108 mg twice daily.
No serious treatment-emergent adverse events were observed. 10 patients discontinued treatment due to treatment-emergent adverse events. The most common of these were constipation, nausea, somnolence, headache, dizziness, and fatigue.
Topline data: https://www.trevitherapeutics.com/wp-content/uploads/2025/09/Smith-et-al.-ERS-Congress-2025-RIVER-Primary.pdf
Responder analysis: https://www.trevitherapeutics.com/wp-content/uploads/2025/09/Smith-et-al.-ERS-Congress-2025-RIVER-Responder-Analysis.pdf
This drug is investigational and its safety and effectiveness have not been established by the FDA.
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