Idiopathic Pulmonary Fibrosis (IPF)-Related Chronic Cough Reduction With Nalbuphine (NAL) Extended-Release (ER) Tablets (OCEAN-2)

A Randomized, Double-Blind, Placebo-Controlled Twelve-Week Fixed-Dose 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 IPF.

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 201
• 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
  • Alabama
    • Tuscaloosa, Alabama, United States, 35476
      • Recruiting
      • Sec Clinical Research - Dothan
  • Connecticut
    • New Britain, Connecticut, United States, 06051
      • Recruiting
      • Starling Physicians, P.C.
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Recruiting
      • Premier Medical Associates, LLC
  • Florida
    • Doral, Florida, United States, 33122
      • Recruiting
      • D&H Doral Research Center
    • Miami, Florida, United States, 33186
      • Recruiting
      • Coral Research Clinic Corp.
    • Miami, Florida, United States, 33173
      • Recruiting
      • Blessed Health Care and Research Inc.
    • Miami Lakes, Florida, United States, 33016
      • Recruiting
      • Pharma Medical Innovations, Inc.
    • North Miami Beach, Florida, United States, 33162
      • Recruiting
      • Essential Health and Research Services
  • Maryland
    • Rockville, Maryland, United States, 20854
      • Recruiting
      • Velocity Clinical Research - Rockville
  • Michigan
    • Allen Park, Michigan, United States, 48101
      • Recruiting
      • Vitalis Clinical Research Center LLC
  • Missouri
    • Warren, Missouri, United States, 48071
      • Recruiting
      • Veritas Clinical Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Recruiting
      • American Health Research - Charlotte Location
  • Oregon
    • Bend, Oregon, United States, 97701
      • Recruiting
      • Summit Health (Summit Medical Group) - Eastside Clinic
    • Portland, Oregon, United States, 97220
      • Recruiting
      • The Oregon Clinic - Gateway Medical Office Location - Pulmonary, Critical Care & Sleep Medicine East
  • Texas
    • Carrollton, Texas, United States, 75010
      • Recruiting
      • Stryde Research
    • Sugar Land, Texas, United States, 77478
      • Recruiting
      • Hillcroft Medical Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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.
• If currently taking antifibrotic medication (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 8 weeks prior to Screening.

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 12 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 12 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 14 for NAL ER Compared With Placebo	Baseline, Week 14

Secondary Outcome Measures

Outcome Measure	Time Frame
Absolute Change from Baseline in the Cough Severity Numerical Rating Scale (CS-NRS) at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Relative Change from Baseline in 24-hour Cough Frequency for NAL ER Compared With Placebo	Baseline, Weeks 6 and 10
Absolute Change from Baseline in 24-hour Cough Frequency for NAL ER Compared With Placebo	Baseline, Weeks 6 and 10
Proportion of Participants Achieving ≥30%, ≥50% and ≥75% Reduction from Baseline in 24-hour Cough Frequency at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in the Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E:RS-IPF) Cough Domain at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in the E-RS:IPF Total Score and Domain Scores (IPF-Breathlessness, IPF-Cough, IPF-Sputum, and IPF-Chest Symptoms) at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in the CS-NRS for NAL ER Compared With Placebo	Baseline up to Week 14
Proportion of Participants Achieving a ≥3-point Improvement from Baseline in CS-NRS for NAL ER Compared With Placebo	Baseline up to Week 14
Absolute Change from Baseline in the Leicester Cough Questionnaire (LCQ) Total Scores at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Proportion of Participants Achieving a 1.3-point Increase (Improvement) from Baseline in LCQ Total Score at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Change from Baseline in the European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L) at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Relative Change from Baseline in Awake Cough Frequency at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Relative Change from Baseline in Sleep Cough Frequency at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in the Patient Global Impression of Severity (PGI-S) Cough Score at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Absolute Change from Baseline in the Patient Global Impression of Change (PGI-C) Cough Score at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Proportion of Participants with Improvements by ≥1 and ≥2 Categories from Baseline on the PGI-S Cough at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Relative Change from Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) at Week 14 for NAL ER Compared With Placebo	Baseline, Week 14
Safety and Tolerability as Assessed by Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Baseline up to Week 17

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: October 5, 2026
• First Submitted That Met QC Criteria: October 5, 2026
• First Posted (Actual): October 9, 2026

Study Record Updates

• Last Update Posted (Actual): November 13, 2026
• Last Update Submitted That Met QC Criteria: November 12, 2026
• Last Verified: November 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: NAL03-302

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