Cough Reduction in IPF With Nalbuphine ER

NCT05964335 | Completed Phase 2 FDA Drug

• 1 other identifier: NAL03-202
• Study Type: interventional
• Target: 165
• Locations: 10 countries
• Sites: 59

Brief Summary

The main purpose of the study is to evaluate the effect of NAL ER on 24-hour cough frequency using objective digital cough monitoring and to assess safety and tolerability of NAL ER.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Cough; Nalbuphine

Outcome Measures

Primary Outcomes (1)

• Relative Change From Baseline in 24-hour Cough Frequency at Week 6

  Baseline, Week 6

Secondary Outcomes (25)

• Change From Baseline in Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E-RS:IPF) Cough subscale at Week 6

  Baseline, Week 6

• Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to Week 12

• Relative Change From Baseline in 24-hour Cough Frequency at Weeks 2,4, and 6

  Baseline, Weeks 2, 4, and 6

• Percentage of Responders With ≥30%, ≥50% and ≥75% Reduction in the 24-Hour Cough Frequency at Week 2, 4, and 6

  At Weeks 2, 4, and 6

• Relative Change From Baseline in Awake Cough Frequency at Week 2, 4, and 6

  Baseline, Weeks 2, 4, and 6

Study Arms (4)

NAL ER 27 mg

EXPERIMENTAL

BID

Drug: NAL ER

NAL ER 54 mg

EXPERIMENTAL

BID

Drug: NAL ER

NAL ER 108 mg

EXPERIMENTAL

BID

Drug: NAL ER

Placebo

PLACEBO COMPARATOR

Placebo, BID

Drug: Placebo

Interventions

NAL ER DRUG

Oral tablets

Also known as: Nalbuphine

NAL ER 27 mg

Placebo DRUG

Oral tablets

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of IPF as determined by the Principal Investigator based on ATS/ERS/JRS/ALAT guidelines.
• Cough Severity Score ≥ 4 on CS-NRS (Cough Severity Numerical Rating Scale) during the Screening period and Baseline.
• History of chronic cough for at least 8 weeks before screening.
• SpO2 ≥ 92%, taken after at least 5 minutes in a sitting position, undisturbed and non-stimulated (Saturation of Hemoglobin with Oxygen as Measured by Pulse Oximetry).
• FVC ≥ 40% predicted of normal - Forced Vital Capacity, as determined by spirometry adhering to ATS/ERS guidelines.
• DLCO ≥ 25% predicted of normal - Diffusing capacity of the lung for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening.

You may not qualify if:

• Currently on continuous oxygen therapy for longer than 16 hours at any level or delivered by any modality. Intermittent oxygen use of any duration over any given 24-hour period is allowed.
• Inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 mL) of water without coughing or choking.
• Upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit.
• Clinical history of aspiration pneumonitis.
• Diagnosis of sleep apnea.
• Abnormal kidney or liver functions based on Screening lab results.
• Known hypersensitivity to nalbuphine or to NAL ER excipients
• History of major psychiatric disorder.
• History of substance abuse.
• Significant medical condition or other factors that may interfere with the participant's ability to successfully complete the study.
• Pregnant or lactating female participant.
• Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug.
• Use of opiates is prohibited within 14 days prior to the baseline visit.
• Use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study.
• Monoamine oxidase inhibitors (MAOIs) including methylene blue (methylthioninium chloride) and the antibiotic linezolid are prohibited within 14 days prior to the baseline visit and for the duration of the study.

Sponsors & Collaborators

• Trevi Therapeutics: lead

Study Sites (59)

Eastern Health-Box Hill Hospital

Box Hill, 3128, Australia

Location

Concord Repatriation General Hospital

Concord, 2139, Australia

Location

Austin Hospital

Heidelberg, 3084, Australia

Location

Respiratory Clinical Trials Pty Ltd

Kent Town, 5067, Australia

Location

TrialsWest Pty Ltd

Spearwood, 6163, Australia

Location

Westmead Hospital

Westmead, 2145, Australia

Location

CIC Mauricie Inc.

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Dynamic Drug Advancement

Ajax, L1S 2J5, Canada

Location

Centre for Lung Health Clinic

Vancouver, V5Z 1M9, Canada

Location

The Pacific Lung Health Centre - St. Pauls Hospital

Vancouver, V6Z 1Y6, Canada

Location

Hospital Clinico Regional Dr. Guillermo Grant Benavente

Concepción, 4040324, Chile

Location

Centro de Investigaciones Medicas Cemedin Ltda.

Quillota, 2260877, Chile

Location

Clinica Universidad de los Andes

Santiago, 7620157, Chile

Location

Centro de Investigacion del Maule

Talca, 3467384, Chile

Location

Hospital Carlos Van Buren

Valparaíso, 2352499, Chile

Location

Oncocentro APYS

Viña del Mar, 2520598, Chile

Location

Universitatsklinik Ruhrlandklinik, Westdeutsches Lungenzentrum

Essen, 45239, Germany

Location

IKF Institut fuer klinische Forschung Frankfurt

Frankfurt am Main, 60596, Germany

Location

Medizinische Hochschule Hannover, Hannover Medical School

Hanover, 30625, Germany

Location

University Hospital of Leipzig

Leipzig, 04103, Germany

Location

IKF Pneumologie Mainz, Helix Medical Excellence Center Mainz

Mainz, 55128, Germany

Location

University Medical Center of Johannes Gutenberg-University Mainz

Mainz, 55131, Germany

Location

Krankenhaus Bethanien

Solingen, 42699, Germany

Location

Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele- Ospedale Gaspare Rodolico

Catania, 95123, Italy

Location

Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia

Foggia, 71122, Italy

Location

Azienda Ospedaliera San Gerardo di Monza

Monza, 20900, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Rome, 00168, Italy

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Martini Ziekenhuis

Groningen, 9728 NT, Netherlands

Location

Erasmus Medisch Centrum 1

Rotterdam, 3015 GD, Netherlands

Location

HMC (Haaglanden Medisch Centrum) Bronovo

The Hague, 2512 VA, Netherlands

Location

Uniwersyteckie Centrum Kliniczne (UCK)

Gdansk, 80-214, Poland

Location

Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego

Lodz, 90-153, Poland

Location

Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie

Olsztyn, 10-357, Poland

Location

Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie

Szczecin, 70-891, Poland

Location

Clinica Mi Tres Torres Barcelona

Barcelona, 08017, Spain

Location

Hospital Universitari de Bellvitge

Barcelona, 08907, Spain

Location

Hospital La Milagrosa

Madrid, 28010, Spain

Location

HUMV

Santander, 39008, Spain

Location

Gulhane Askeri Tip Akademisi (GATA) - Gulhane Askeri Tip Fakultesi (Gulhane Military Medical Academy and Medical School)

Ankara, 06010, Turkey (Türkiye)

Location

Akdeniz University Faculty of Medicine

Antalya, 7070, Turkey (Türkiye)

Location

Canakkale Onsekiz Mart Universitesi (COMU) - Tip Fakultesi Hastanesi

Çanakkale, 17020, Turkey (Türkiye)

Location

Sureyyapasa Gogus Hastaliklari ve Gogus Cerrahisi Egitim ve Arastirma Hastanesi

Istanbul, 34854, Turkey (Türkiye)

Location

Ege University Medical Faculty

Izmir, 35100, Turkey (Türkiye)

Location

Selcuk Universty Medical Faculty

Konya, 42130, Turkey (Türkiye)

Location

Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2GW, United Kingdom

Location

Royal Papworth Hospital

Cambridge, CB2 0AY, United Kingdom

Location

Hull and East Yorkshire - Castle Hill Hospital

Cottingham, HU16 5JQ, United Kingdom

Location

Royal Infirmary Of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

University College London

London, NW1 2PG, United Kingdom

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Altnagelvin Area Hospital

Londonderry, BT47 6SB, United Kingdom

Location

Wythenshawe Hospital

Manchester, M23 9LT, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Southern Health & Social Care Trust, Craigavon Area Hospital

Portadown, BT63 5QQ, United Kingdom

Location

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Molyneaux PL, Mogulkoc N, Gunen H, Doboszynska A, Kreuter M, Neustifter B, Mathur V, Cassella J; CORAL Study Group. Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial. JAMA. 2026 Jan 22. doi: 10.1001/jama.2025.26179. Online ahead of print.

  PMID: 41569557 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Cough

Interventions

Nalbuphine

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Chief Development Officer

  Trevi Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 27, 2023
• Study Start: February 6, 2024
• Primary Completion: April 24, 2025
• Study Completion: April 24, 2025
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (6); NL (4); IT (5); PL (4); ES (4); GB (13); CA (4); CL (6); TU (6); DE (7)