Trevi Therapeutics has published positive Phase 2b results from its CORAL trial evaluating oral nalbuphine ER for chronic cough in patients with idiopathic pulmonary fibrosis (IPF). The study was published in JAMA, validating both the data quality and clinical relevance.
Key efficacy outcomes from the CORAL trial
Nalbuphine ER demonstrated statistically significant cough reduction versus placebo.
Highlights at Week 6:
- Significant reduction in 24-hour objective cough frequency across all dose groups
- Cough reduction observed as early as Week 2, the first measured time point
- Over 60% of treated patients achieved ≥50% reduction in cough frequency
Patient-reported cough outcomes aligned closely with objective cough monitoring data.
Consistency across objective and patient-reported outcomes
The trial showed strong concordance between:
- Objective cough frequency monitoring
- Patient-reported cough assessments
This confirms that patients experienced both measurable and perceived symptom improvement.
Investigator perspective: addressing a major unmet need
“Chronic cough imposes a significant burden on patients with IPF,” said Dr. Philip Molyneaux, Royal Brompton Hospital, London. “The consistency between objective and patient-reported outcomes is particularly encouraging.”
Safety profile remains consistent
Nalbuphine ER was generally well tolerated. Safety observations:
- Discontinuation due to adverse events:
- Nalbuphine ER: 5.6%
- Placebo: 5.0%
- Most common adverse events:
- Nausea, vomiting, constipation
- Dizziness, headache, fatigue
- Somnolence, dry mouth
Serious adverse events were fewer in nalbuphine ER-treated patients than placebo.
Why chronic cough in IPF matters?
- ~150,000 IPF patients in the US
- ~two-thirds experience uncontrolled chronic cough
- Patients may cough up to 1,500 times per day
Chronic cough worsens quality of life and may increase morbidity and disease progression risk. There are no FDA-approved therapies for IPF-related chronic cough.
CORAL trial design at a glance
- Phase 2b, randomized, double-blind, placebo-controlled
- 165 IPF patients with chronic cough
- Nalbuphine ER doses: 27 mg, 54 mg, 108 mg BID
- Treatment duration: 6 weeks
- Primary endpoint: Relative change in 24-hour cough frequency vs baseline
About nalbuphine ER (Haduvio™)
- Oral extended-release formulation
- Acts centrally and peripherally on the cough reflex arc
- Kappa agonist and mu antagonist (KAMA) mechanism
- Not scheduled by the US DEA
Trevi plans to commercialize nalbuphine ER under the trade name Haduvio™.
