The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC) (LAKE)

August 5, 2026 updated by: Trevi Therapeutics

A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Study to Evaluate the Efficacy and Safety of Nalbuphine Extended-Release Tablets for the Treatment of Participants With Refractory Chronic Cough

The purpose of this study is to evaluate the efficacy and safety of Nalbuphine ER Extended-release tablets for the treatment of participants with RCC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Connie Crum

Study Locations

  • Canada
      • Ajax, Canada, L1S 2J5
        • Recruiting
        • Dynamic Drug Advancement Ltd
      • Burlington, Canada, L7N3V2
        • Recruiting
        • BLC Clinical Research
      • Montreal, Canada, H1Y3H5
        • Recruiting
        • Recherche GCP Research
      • North Van Couver, Canada, V7P2T4
        • Recruiting
        • Medical Arts Health Research Group - North Vancouver
      • Québec, Canada, G1V4T3
        • Recruiting
        • Diex Recherche - Quebec
      • Québec, Canada, G1V4W2
        • Recruiting
        • Clinique Specialisee En Allergie De La Capitale
      • Saint-Charles-Borromée, Canada, J6E 2B4
        • Recruiting
        • Clinque DE Pneumologie ET Du Sommeil DE Lanaudiere
      • Trois-Rivières, Canada, G8T7A1
        • Recruiting
        • Centre D'Investigation Clinique Mauricie Inc (CIC Mauricie)
      • Victoriaville, Canada, G6P3Z8
        • Recruiting
        • Diex Recherche-Victoriaville
      • Waterloo, Canada, N2J1C4
        • Recruiting
        • Fadia El Boreky Medicine Prof. Corp.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Meets society guideline-based criteria for a diagnosis of RCC defined as:

    • Insufficient improvement in cough after treatment for any identified cough-associated conditions.
    • Unexplained cough for which an underlying condition has not been determined despite adequate investigation with diagnostic tests and trials of therapy.
  • Persistent and chronic cough for at least one year prior to Screening.
  • Chest computed tomography (CT) or chest radiograph of the thorax performed within the last 24 months and after the onset of chronic cough OR the procedure completed by the Investigator during the Screening period, that does not show any abnormality considered to be significantly contributing to the RCC in the opinion of the Principal Investigator.
  • 24-hour objective cough frequency ≥10 coughs/hour based on VitaloJAK® cough monitor recording performed during the Screening and Placebo Run-in Periods as well as a minimum recording duration of 20 hours suitable for analysis during the placebo Run-in assessment.
  • Forced expiratory volume in 1 second (FEV1) /forced vital capacity (FVC) ratio ≥ 60% as determined by spirometry adhering to American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines.

Exclusion Criteria:

  • Clinical diagnosis of sleep apnea and/or use of continuous positive airway pressure (CPAP).
  • Upper or lower respiratory tract infection or change in pulmonary status in the 4 weeks prior to the Screening visit or during the Screening or PBO Run-in periods.
  • History of bronchiectasis, chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), or other significant respiratory disorder that might affect cough.

  • History of uncontrolled asthma defined as one of the following:

    • ≥1 clinically significant exacerbation in the last 6 months, OR
    • ≥2 clinically significant exacerbations in the past 12 months (a clinically significant asthma exacerbation is defined as requiring the use of systemic corticosteroids).
  • Current smoker or vaper or current use of tobacco smoke, cannabis smoke, or nicotine vaper.
  • Individuals who have stopped smoking or vaping within the past 6 months, or those with >20 pack-year smoking history.
  • Current active tuberculosis or nontuberculous mycobacterial infection, a history of latent untreated tuberculosis, or a history of incompletely treated tuberculosis.
  • Speech therapy/physiotherapy for RCC starting within 4 weeks of Baseline or during the study. Speech therapy/physiotherapy is acceptable if the participant has started the therapy more than 4 weeks prior to the Baseline visit AND plans to continue the therapy through the Titration and Fixed-dose Treatment Period.
  • Known intolerance [gastrointestinal, central nervous system (CNS) symptoms], hypersensitivity, or drug allergy considered to be related to an opioid drug or known hypersensitivity to nalbuphine or to NAL ER excipients.

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NAL ER 54 mg BID
Participants will receive NAL ER during the titration period, with dose titration starting at 27 milligrams (mg) once daily (QD) and increasing up to 54 mg twice daily (BID) from Day 1 to Day 14. Participants will receive NAL ER 54 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
Drug: Placebo
Oral tablets
Drug: NAL ER
Oral tablets
Other Names:
  • Nalbuphine
Experimental: NAL ER 27 mg BID
Participants will receive NAL ER during the titration period, starting at 27 mg QD to 27 mg BID from Day 1 to Day 14. Participants will receive NAL ER 27 mg BID during the fixed-dose treatment period from Day 15 to Day 42.
Drug: Placebo
Oral tablets
Drug: NAL ER
Oral tablets
Other Names:
  • Nalbuphine
Experimental: NAL ER 27 mg QD
Participants will receive NAL ER 27 mg QD during the titration period from Day 1 to Day 14. Participants will continue to receive NAL ER 27 mg QD during the fixed-dose treatment period from Day 15 to Day 42.
Drug: Placebo
Oral tablets
Drug: NAL ER
Oral tablets
Other Names:
  • Nalbuphine
Placebo Comparator: Placebo
Participants will receive matching placebo during the titration period from Day 1 to Day 14 and the fixed-dose treatment period from Day 15 to Day 42.
Drug: Placebo
Oral tablets

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
Time Frame: Baseline, Week 6
Baseline, Week 6

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6
Time Frame: Baseline, Week 6
Baseline, Week 6
Relative Change From Baseline in 24-hour Cough Frequency
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Percentage of Participants Achieving ≥30%, ≥50% and ≥75% Reduction in 24-hour Cough Frequency
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in Patient Reported Cough Frequency (PR-CF)
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in Cough Severity Visual Analog Scale (CS-VAS)
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Percentage of Participants Achieving a 30 Millimeter (mm) Improvement in CS-VAS Total Score
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS)
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in McMaster Cough Severity Questionnaire (MCSQ) Total Score
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in MCSQ Domains (Intensity and Frequency)
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 6
Time Frame: Baseline, Week 6
Baseline, Week 6
Percentage of Participants Achieving a 1.3- Point Increase From Baseline in LCQ Total Score at Week 6
Time Frame: Baseline, Week 6
Baseline, Week 6
Relative Change From Baseline in Awake Cough Frequency
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Relative Change From Baseline in Sleep Cough Frequency
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough Score
Time Frame: Baseline up to Week 6
Baseline up to Week 6
Mean Patient Global Impression of Change for Cough (PGI-C) Cough Score
Time Frame: Up to Week 6
Up to Week 6
Change From Baseline in International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) Score at Week 6
Time Frame: Baseline, Week 6
Baseline, Week 6
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time Frame: Up to Day 63
Up to Day 63

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Trevi Therapeutics

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Chief Development Officer, Trevi Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 22, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 22, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 22, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 26, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 5, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NAL04-202
  • 2026-526087-20-00 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings