Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05964335




Registration number
NCT05964335
Ethics application status
Date submitted
7/07/2023
Date registered
27/07/2023
Date last updated
27/06/2025

Titles & IDs
Public title
Cough Reduction in IPF With Nalbuphine ER
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Parallel, 4-Arm Dose Ranging Study of the Safety and Efficacy of Nalbuphine Extended-Release Tablets (NAL ER) for the Treatment of Cough in Idiopathic Pulmonary Fibrosis (IPF)
Secondary ID [1] 0 0
NAL03-202
Universal Trial Number (UTN)
Trial acronym
CORAL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Idiopathic Pulmonary Fibrosis 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NAL ER
Treatment: Drugs - Placebo
Treatment: Drugs - NAL ER
Treatment: Drugs - NAL ER

Experimental: NAL ER 27 mg - BID

Experimental: NAL ER 54 mg - BID

Experimental: NAL ER 108 mg - BID

Placebo comparator: Placebo - Placebo, BID


Treatment: Drugs: NAL ER
Oral tablets

Treatment: Drugs: Placebo
Oral tablets

Treatment: Drugs: NAL ER
Oral Tablets

Treatment: Drugs: NAL ER
Oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Relative Change From Baseline in 24-hour Cough Frequency at Week 6
Timepoint [1] 0 0
Baseline, Week 6
Secondary outcome [1] 0 0
Change From Baseline in Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E-RS:IPF) Cough subscale at Week 6
Timepoint [1] 0 0
Baseline, Week 6
Secondary outcome [2] 0 0
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Timepoint [2] 0 0
Up to Week 12
Secondary outcome [3] 0 0
Relative Change From Baseline in 24-hour Cough Frequency at Weeks 2,4, and 6
Timepoint [3] 0 0
Baseline, Weeks 2, 4, and 6
Secondary outcome [4] 0 0
Percentage of Responders With =30%, =50% and =75% Reduction in the 24-Hour Cough Frequency at Week 2, 4, and 6
Timepoint [4] 0 0
At Weeks 2, 4, and 6
Secondary outcome [5] 0 0
Relative Change From Baseline in Awake Cough Frequency at Week 2, 4, and 6
Timepoint [5] 0 0
Baseline, Weeks 2, 4, and 6
Secondary outcome [6] 0 0
Relative Change From Baseline in Sleep Cough Frequency at Week 2, 4, and 6
Timepoint [6] 0 0
Baseline, Weeks 2, 4, and 6
Secondary outcome [7] 0 0
Change From Baseline in E-RS: IPF Cough Subscale at Weeks 1, 2, 3, 4, 5, and 6
Timepoint [7] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, 6
Secondary outcome [8] 0 0
Percentage of E-RS: IPF Cough Subscale Responders With At least one Category Improvement at Weeks 1, 2, 3, 4, 5, and 6
Timepoint [8] 0 0
At Weeks 1, 2, 3, 4, 5, and 6
Secondary outcome [9] 0 0
Change From Baseline in E-RS: IPF Total Score, Subdomain Scores (IPF-Breathlessness, IPF-Cough, IPF-Sputum, and IPF-Chest Symptoms) and Individual Items at Weeks 1, 2, 3, 4, 5, and 6
Timepoint [9] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, and 6
Secondary outcome [10] 0 0
Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS) at Weeks 1, 2, 3, 4, 5, and 6
Timepoint [10] 0 0
Baseline, Weeks 1, 2, 3, 4, 5, and 6
Secondary outcome [11] 0 0
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6
Timepoint [11] 0 0
Baseline, Week 6
Secondary outcome [12] 0 0
Percentage of LCQ Total Score Responders With 1.3-Point Increase Response at Week 6
Timepoint [12] 0 0
At Week 6
Secondary outcome [13] 0 0
Change From Baseline in LCQ Domains and Individual Items at Week 6
Timepoint [13] 0 0
Baseline, Week 6
Secondary outcome [14] 0 0
Change From Baseline in Living With Pulmonary Fibrosis Impacts Questionnaire (L-IPF©) at Week 6
Timepoint [14] 0 0
Baseline, Week 6
Secondary outcome [15] 0 0
Change From Baseline in Living With Pulmonary Fibrosis Symptoms Questionnaire (L-IPF) and its Domains at Week 6
Timepoint [15] 0 0
Baseline, Week 6
Secondary outcome [16] 0 0
Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L™) at Week 6
Timepoint [16] 0 0
Baseline, Week 6
Secondary outcome [17] 0 0
Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough at Weeks 2, 4, and 6
Timepoint [17] 0 0
Baseline, Weeks 2, 4, and 6
Secondary outcome [18] 0 0
Absolute Values of PGI-C Cough Score at Weeks 2, 4, and 6
Timepoint [18] 0 0
At Weeks 2, 4, and 6
Secondary outcome [19] 0 0
Percentage of Participants With Improvement by =1 and =2 Categories, Worsening by =1 and =2 Categories, and no Change on PGI-C and PGI-S Cough at Each Post-Baseline Timepoint
Timepoint [19] 0 0
At Weeks 2, 4, and 6
Secondary outcome [20] 0 0
Change from Baseline in PGI-S IPF at Weeks 2, 4, and 6
Timepoint [20] 0 0
Baseline, Weeks 2, 4, and 6
Secondary outcome [21] 0 0
Absolute Values of PGI-C IPF at Weeks 2, 4, and 6
Timepoint [21] 0 0
At Weeks 2, 4, and 6
Secondary outcome [22] 0 0
Percentage of Participants With Improvement by =1 and =2 Categories, Worsening by =1 and =2 Categories, and no Change on the PGI-C and PGI-S IPF at Weeks 2, 4, and 6
Timepoint [22] 0 0
At Weeks 2, 4, and 6
Secondary outcome [23] 0 0
Change From Baseline in Clinicians Global Impression of Severity (CGI-S) score at Week 6
Timepoint [23] 0 0
Baseline, Week 6
Secondary outcome [24] 0 0
Absolute Values for CGI-C IPF Score at Week 6
Timepoint [24] 0 0
At Week 6
Secondary outcome [25] 0 0
Percentage of Participants With Improvement by =1 and =2 Categories, Worsening by =1 and =2 Categories, and no Change on the CGI-C and CGI-S at Week 6
Timepoint [25] 0 0
At Week 6

Eligibility
Key inclusion criteria
* 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.
* Use of oral corticosteroid cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
* Exposure to any investigational medication, including placebo, is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
* Medications prescribed as cough suppressants are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
* Use of medications that affect serotonergic neurotransmission and that when used concomitantly with opioids can increase the risk of serotonin syndrome are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
* Anti-fibrotic medications are prohibited unless on a stable dose for 8 weeks prior to the baseline visit and are expected to remain on that dose for the duration of the study.
* Strong inhibitors/inducers of the P450 Isozymes are prohibited unless on a stable dose for 14-days prior to baseline visit and are expected to remain on that dose for the duration of the study.
* Use of a medication having a "known risk" of Torsade de Pointes (categorized as "KR" on the Credible Meds® website.) 4 weeks prior to Baseline.
* Use of unstable doses of medications associated with a potential risk of QT prolongation but not clearly associated with Torsade de Pointes within 4 weeks of screening.

Other protocol defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/02/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/04/2025
Sample size
Target
Accrual to date
Final
165
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Eastern Health-Box Hill Hospital - Box Hill
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Respiratory Clinical Trials Pty Ltd - Kent Town
Recruitment hospital [5] 0 0
TrialsWest Pty Ltd - Spearwood
Recruitment hospital [6] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
5067 - Kent Town
Recruitment postcode(s) [5] 0 0
6163 - Spearwood
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Quebec
Country [2] 0 0
Canada
State/province [2] 0 0
Ajax
Country [3] 0 0
Canada
State/province [3] 0 0
Vancouver
Country [4] 0 0
Chile
State/province [4] 0 0
Concepcion
Country [5] 0 0
Chile
State/province [5] 0 0
Quillota
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
Chile
State/province [7] 0 0
Talca
Country [8] 0 0
Chile
State/province [8] 0 0
Valparaiso
Country [9] 0 0
Chile
State/province [9] 0 0
Vina del Mar
Country [10] 0 0
Germany
State/province [10] 0 0
Essen
Country [11] 0 0
Germany
State/province [11] 0 0
Frankfurt am Main
Country [12] 0 0
Germany
State/province [12] 0 0
Hannover
Country [13] 0 0
Germany
State/province [13] 0 0
Leipzig
Country [14] 0 0
Germany
State/province [14] 0 0
Mainz
Country [15] 0 0
Germany
State/province [15] 0 0
Solingen
Country [16] 0 0
Italy
State/province [16] 0 0
Catania
Country [17] 0 0
Italy
State/province [17] 0 0
Foggia
Country [18] 0 0
Italy
State/province [18] 0 0
Monza
Country [19] 0 0
Italy
State/province [19] 0 0
Padua
Country [20] 0 0
Italy
State/province [20] 0 0
Rome
Country [21] 0 0
Netherlands
State/province [21] 0 0
's-Hertogenbosch
Country [22] 0 0
Netherlands
State/province [22] 0 0
Den Haag
Country [23] 0 0
Netherlands
State/province [23] 0 0
Groningen
Country [24] 0 0
Netherlands
State/province [24] 0 0
Rotterdam
Country [25] 0 0
Poland
State/province [25] 0 0
Gdansk
Country [26] 0 0
Poland
State/province [26] 0 0
Lodz
Country [27] 0 0
Poland
State/province [27] 0 0
Olsztyn
Country [28] 0 0
Poland
State/province [28] 0 0
Szczecin
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Santander
Country [32] 0 0
Turkey
State/province [32] 0 0
Ankara
Country [33] 0 0
Turkey
State/province [33] 0 0
Antalya
Country [34] 0 0
Turkey
State/province [34] 0 0
Canakkale
Country [35] 0 0
Turkey
State/province [35] 0 0
Istanbul
Country [36] 0 0
Turkey
State/province [36] 0 0
Izmir
Country [37] 0 0
Turkey
State/province [37] 0 0
Konya
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Birmingham
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Cambridge
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Cottingham
Country [41] 0 0
United Kingdom
State/province [41] 0 0
Edinburgh
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Londonderry
Country [43] 0 0
United Kingdom
State/province [43] 0 0
London
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Manchester
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Norwich
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Nottingham
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Oxford
Country [48] 0 0
United Kingdom
State/province [48] 0 0
Portadown
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Trevi Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Chief Development Officer
Address 0 0
Trevi Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Beata Dworakowska
Address 0 0
Country 0 0
Phone 0 0
(203) 304-2499
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT05964335