Trevi Therapeutics (TRVI) Study Result summary

Study Overview and Design

• The Phase II-A RIVER trial was a randomized, double-blind, placebo-controlled, two-period crossover study evaluating Haduvio (oral nalbuphine ER) in 66 patients with refractory chronic cough (RCC), with 59 included in the primary efficacy analysis.

• Patients had a mean age of about 60 years, with 66.7% female and 92.4% white, and were stratified by baseline cough frequency (10–19 or ≥20 coughs/hour).

• Dosing was titrated from 27 mg to 108 mg twice daily, with assessments at days 7, 14, and 21, and a 21-day washout between periods.

• The primary endpoint was the relative change from baseline in 24-hour cough frequency at Day 21, measured objectively using the VitaloJAK device.

• Secondary endpoints included patient-reported cough frequency, cough severity (CS-VAS), and quality of life measures.

Efficacy Results

• Haduvio achieved a 67% reduction in 24-hour cough frequency from baseline and a 57% placebo-adjusted reduction (p<0.0001), with efficacy observed as early as Day 7 at the lowest dose.

• Statistically significant reductions were consistent across both moderate (10–19 coughs/hour) and severe (≥20 coughs/hour) subgroups.

• 84% of patients on the highest dose achieved at least a 30% reduction in cough frequency, and 77% achieved at least a 50% reduction.

• More than half of patients achieved a 75% reduction in cough frequency at the highest dose.

• Haduvio outperformed other RCC therapies, which showed only 12–37% reductions in comparable trials.

Patient-Reported Outcomes and Safety

• Statistically significant improvements in patient-reported cough severity and frequency were seen as early as Day 7, corroborating objective findings.

• The adverse event profile was consistent with prior studies; most common AEs (≥10%) included constipation (28.6%), somnolence (25.4%), nausea (22.2%), dizziness (19.0%), headache (15.9%), and fatigue (14.3%).

• No treatment-emergent serious adverse events were reported; discontinuation due to AEs occurred in about 14.3–15% of patients, compared to 1.7% on placebo.

• Six patients experienced Grade 3 adverse events, but none exceeded this severity.

• The drug is considered easy to use, with tolerability manageable through dose titration and patient education.