Refractory Chronic CoughPhase 2LAKENCT07671924
The Effect of Nalbuphine Extended-Release (NAL ER) on Cough in Participants With Refractory Chronic Cough (RCC)
A Phase 2 study testing NAL ER in people with Refractory Chronic Cough, run by Trevi Therapeutics at 21 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Refractory Chronic Cough
- What is being tested?
- NAL ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 21 sitesin 2 countries
- Study dates
- 22 Jun 2026to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 12Show fewer
- 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.
Trial locations and contacts
21 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 2 countries
Canada11 sites, 11 recruiting
- Recruiting
Dynamic Drug Advancement Ltd
Ajax, L1S 2J5
- Recruiting
BLC Clinical Research
Burlington, L7N3V2
- Recruiting
Kelowna Respirology & Allergy Research
Kelowna, British Columbia, V1Y3H5
- Recruiting
Recherche GCP Research
Montreal, H1Y3H5
- Recruiting
Medical Arts Health Research Group - North Vancouver
North Van Couver, V7P2T4
- Recruiting
Diex Recherche - Quebec
Québec, G1V4T3
- Recruiting
Clinique Specialisee En Allergie De La Capitale
Québec, G1V4W2
- Recruiting
Clinque DE Pneumologie ET Du Sommeil DE Lanaudiere
Saint-Charles-Borromée, J6E 2B4
- Recruiting
Inspiration Research Limited
Toronto, Ontario, M5T3A9
- Recruiting
Centre D'Investigation Clinique Mauricie Inc (CIC Mauricie)
Trois-Rivières, G8T7A1
- Recruiting
Diex Recherche-Victoriaville
Victoriaville, G6P3Z8
United Kingdom10 sites, 10 recruiting
- Recruiting
Ormeau Clinical Trials LTD.
Belfast, BT2 8BG
- Recruiting
West Walk Surgery
Bristol, BS37 4AX
- Recruiting
Hull University Teaching Hospitals NHS Trust - Respiratory Clinical Trials Unit
Cottingham, HU16 5JQ
- Recruiting
Northwick Park Hospital
Harrow, HA1 3UJ
- Recruiting
NIHR Leicester Biomedical Research Centre Leicester General Hospital
Leicester, LE3 9QP
- Recruiting
King's College Hospital (KCH) NHS Foundation Trust - King's College Hospital
London, SE5 9RS
- Recruiting
Manchester University NHS Foundation Trust - Wythenshawe Hospital - North West Lung Centre
Manchester, M23 9LT
- Recruiting
Pier Health Group
North Somerset, BS24 7PR
- Recruiting
The Breckland Alliance - Grove Surgery
Thetford, IP24 1JD
- Recruiting
Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital
Tyne and Wear, NE29 8NH
About this study
Official title: 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.
- Conditions
- Refractory Chronic Cough
- Being tested
- NAL ER, Placebo
- Medical subject headings
- Chronic Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NAL ERDrug
Also called Nalbuphine
Oral tablets
PlaceboDrug
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| NAL ER 54 mg BID | Experimental | 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. Receives: Drug: NAL ER; Drug: Placebo |
| NAL ER 27 mg BID | Experimental | 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. Receives: Drug: NAL ER; Drug: Placebo |
| NAL ER 27 mg QD | Experimental | 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. Receives: Drug: NAL ER; Drug: Placebo |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
Measured: Baseline, Week 6
Secondary outcomes (17)
Relative Change From Baseline in 24-hour Cough Frequency
Measured: Baseline up to Week 6
Percentage of Participants Achieving ≥30%, ≥50% and ≥75% Reduction in 24-hour Cough Frequency
Measured: Baseline up to Week 6
Change From Baseline in Patient Reported Cough Frequency (PR-CF)
Measured: Baseline up to Week 6
Change From Baseline in Cough Severity Visual Analog Scale (CS-VAS)
Measured: Baseline up to Week 6
Percentage of Participants Achieving a 30 Millimeter (mm) Improvement in CS-VAS Total Score
Measured: Baseline up to Week 6
Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS)
Measured: Baseline up to Week 6
Change From Baseline in McMaster Cough Severity Questionnaire (MCSQ) Total Score
Measured: Baseline up to Week 6
Change From Baseline in MCSQ Domains (Intensity and Frequency)
Measured: Baseline up to Week 6
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6
Measured: Baseline, Week 6
Change From Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 6
Measured: Baseline, Week 6
Percentage of Participants Achieving a 1.3- Point Increase From Baseline in LCQ Total Score at Week 6
Measured: Baseline, Week 6
Relative Change From Baseline in Awake Cough Frequency
Measured: Baseline up to Week 6
Relative Change From Baseline in Sleep Cough Frequency
Measured: Baseline up to Week 6
Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough Score
Measured: Baseline up to Week 6
Mean Patient Global Impression of Change for Cough (PGI-C) Cough Score
Measured: Up to Week 6
Change From Baseline in International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) Score at Week 6
Measured: Baseline, Week 6
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Measured: Up to Day 63
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2026
- Study start22 Jun 2026
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Chronic CoughStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trevi Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Development Officer, Study director, Trevi Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07671924
- Sponsor's protocol ID
- NAL04-202
- Other IDs
- 2026-526087-20-00
- Acronym
- LAKE
- Status last verified
- Nov 2026
- First submitted
- 22 Jun 2026
- Last updated
- 5 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07671924
- Acronym / sponsor ID
- LAKE / NAL04-202
- Conditions
- Refractory Chronic Cough
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Trevi TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 22 Jun 2026 (actual)
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 26 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NAL ER 54 mg BID | Experimental | Drug: NAL ER, Drug: PlaceboParticipants 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. |
| NAL ER 27 mg BID | Experimental | Drug: NAL ER, Drug: PlaceboParticipants 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. |
| NAL ER 27 mg QD | Experimental | Drug: NAL ER, Drug: PlaceboParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Meets society guideline-based criteria for a diagnosis of RCC defined as:
- 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.
Key exclusion criteria (12 listed)
- 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:
- Current smoker or vaper or current use of tobacco smoke, cannabis smoke, or nicotine vaper.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NAL ERAlso: NalbuphineOral tablets | Drug | NAL ER 27 mg BID, NAL ER 27 mg QD, NAL ER 54 mg BID |
| PlaceboOral tablets | Drug | NAL ER 27 mg BID, NAL ER 27 mg QD, NAL ER 54 mg BID, Placebo |
Primary outcome
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
Time frame: Baseline, Week 6
17 secondary outcomes
Relative Change From Baseline in 24-hour Cough Frequency
Time frame: 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
Change From Baseline in Patient Reported Cough Frequency (PR-CF)
Time frame: Baseline up to Week 6
Change From Baseline in Cough Severity Visual Analog Scale (CS-VAS)
Time frame: 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
Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS)
Time frame: Baseline up to Week 6
Change From Baseline in McMaster Cough Severity Questionnaire (MCSQ) Total Score
Time frame: Baseline up to Week 6
Change From Baseline in MCSQ Domains (Intensity and Frequency)
Time frame: Baseline up to Week 6
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6
Time frame: Baseline, Week 6
Change From Baseline in Each LCQ Domain Score (Physical, Psychological, Social) at Week 6
Time frame: 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
Relative Change From Baseline in Awake Cough Frequency
Time frame: Baseline up to Week 6
Relative Change From Baseline in Sleep Cough Frequency
Time frame: 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
Mean Patient Global Impression of Change for Cough (PGI-C) Cough Score
Time frame: 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
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Up to Day 63
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Click here to learn more about the participation in this trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Chief Development Officer study director
Trevi Therapeutics
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NAL ER in people with Refractory Chronic Cough, run by Trevi Therapeutics at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paula Buckley ((203) 304-2499, Paula.Buckley@trevitherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relative Change From Baseline in 24-hour Cough Frequency at Week 6 (time frame: Baseline, Week 6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.