Idiopathic Pulmonary Fibrosis (IPF)-Related Chronic Cough Reduction With Nalbuphine Extended-Release (NAL ER) Tablets (OCEAN-1)

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nalbuphine Extended-Release Tablets for the Treatment of Chronic Cough in Participants With Idiopathic Pulmonary Fibrosis

The primary purpose is to evaluate the safety and efficacy of NAL ER for the treatment of chronic cough in participants with Idiopathic Pulmonary Fibrosis (IPF).

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: NAL ER

• Study Type: Interventional
• Enrollment (Estimated): 306
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Paula Buckley; Phone Number: (203) 304-2499; Email: Paula.Buckley@trevitherapeutics.com

Study Locations

• United States
  • Florida
    • Loxahatchee Groves, Florida, United States, 33470
      • Recruiting
      • Pulmonary Specialists of The Palm Beaches
    • Miami, Florida, United States, 33126
      • Recruiting
      • Clinical Research and Associates, Inc.
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Recruiting
      • Clinical Research of Gastonia (CRG)
  • Texas
    • El Paso, Texas, United States, 79902
      • Recruiting
      • El Paso Pulmonary Association, PA
    • Houston, Texas, United States, 77058
      • Recruiting
      • Elevate Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of IPF as determined by the Investigator based on American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Society (ALAT) clinical practice guidelines.
• Chronic cough for ≥8 weeks prior to Screening.
• PGI-Severity Score ≥ 2 at Screening.
• Forced vital capacity (FVC) ≥40 percent (%) of predicted at Screening.
• Diffusing capacity for carbon monoxide (DLCO) ≥25% of predicted during Screening or within 12 weeks prior to Screening.
• Participants who are currently taking antifibrotic medication (e.g., nintedanib, pirfenidone, nerandomilast) should be on a stable dose for at least 6 weeks prior to the Baseline Visit.

Exclusion Criteria:

• Clinical diagnosis or clinical suspicion of an upper or lower respiratory tract infection in the last 8 weeks prior to the Screening visit or during Screening.
• Hospitalization for any respiratory illness (including acute exacerbation of IPF) within 2 months prior to Screening.
• Diagnosed sleep apnea or currently on any treatment for sleep apnea [example (e.g.), Continuous Positive Airway Pressure (CPAP)].

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NAL ER 54 mg; Participants will undergo a 2-week blinded titration period followed by a fixed dose treatment period receiving NAL ER 54 milligrams (mg) twice daily (BID) for 52 weeks.	Drug: NAL ER; Oral tablets; Other Names: Nalbuphine
Placebo Comparator: Placebo; Participants will undergo a 2-week blinded titration period followed by a fixed dose treatment period receiving a matching placebo BID for 52 weeks.	Drug: Placebo; Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Relative Change from Baseline in 24-hour Cough Frequency at Week 26	Baseline, Week 26

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute Change from Baseline in the Cough Severity Numerical Rating Scale (CS-NRS) at Week 26	Baseline, Week 26
Relative Change from Baseline in 24-hour Cough Frequency at Week 6	Baseline, Week 6
Percentage of Participants Achieving ≥50% Reduction from Baseline in 24-hour Cough Frequency at Week 26	Baseline, Week 26
Absolute Change from Baseline in the Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E:RS-IPF) Cough Domain at Week 26	Baseline, Week 26
Percentage of Participants Achieving a ≥3-point Improvement from Baseline in CS-NRS at Week 26	Baseline, Week 26
Absolute Change from Baseline in the E:RS IPF Breathlessness Domain at Week 26	Baseline, Week 26
Relative Change from Baseline in 24-hour Cough Frequency	Baseline up to Week 54
Percentage of Participants Achieving ≥30%, ≥50% and ≥75% Reduction from Baseline in 24-Hour Cough Frequency	Baseline up to Week 54
Absolute Change from Baseline in the E-RS:IPF Cough Domain	Baseline up to Week 54
Absolute Change from Baseline in the E-RS:IPF Total Score and Domain Scores (IPF-Breathlessness, IPF-Cough, IPF-Sputum, and IPF-Chest Symptoms)	Baseline up to Week 54
Absolute Change from Baseline in the CS-NRS	Baseline up to Week 54
Percentage of Participants Achieving a ≥3-Point Improvement from Baseline in CS-NRS	Baseline up to Week 54
Absolute Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Scores	Baseline up to Week 54
Percentage of Participants Achieving a 1.3-Point Increase (Improvement) from Baseline in LCQ Total Score	Baseline up to Week 54
Absolute Change from Baseline in Each LCQ Domain Score (Physical, Psychological, Social)	Baseline up to Week 54
Change from Baseline in the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) at Week 26	Baseline, Week 26
Relative Change from Baseline in Awake Cough Frequency	Baseline up to Week 54
Relative Change from Baseline in Sleep Cough Frequency	Baseline up to Week 54
Absolute Change from Baseline in the Patient Global Impression of Severity (PGI-S) Cough Score	Baseline up to Week 54
Absolute Change from Baseline in the Patient Global Impression of Change (PGI-C) Cough Score	Baseline up to Week 54
Percentage of Participants with Improvements by ≥1 and ≥2 Categories from Baseline on the PGI-S Cough	Baseline up to Week 54
Safety and Tolerability as Assessed by Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Up to Week 57

Collaborators and Investigators

• Sponsor: Trevi Therapeutics
• Investigators: Study Director: Chief Development Officer, Trevi Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 26, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 9, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Nalbuphine
• Other Study ID Numbers: NAL03-301; 2026-525877-38-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes