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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05964335




Registration number
NCT05964335
Ethics application status
Date submitted
7/07/2023
Date registered
27/07/2023
Date last updated
24/05/2024

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 - nalbuphine ER 27 mg
Treatment: Drugs - Placebo
Treatment: Drugs - nalbuphine ER 54 mg
Treatment: Drugs - nalbuphine ER 108 mg

Experimental: NAL ER 27 mg - BID

Experimental: NAL ER 54 mg - BID

Experimental: NAL ER 108 mg - BID

Placebo Comparator: Placebo - Placebo, tablets BID


Treatment: Drugs: nalbuphine ER 27 mg
Oral tablets

Treatment: Drugs: Placebo
Oral tablets

Treatment: Drugs: nalbuphine ER 54 mg
Oral Tablets

Treatment: Drugs: nalbuphine ER 108 mg
Oral tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Effect of NAL ER on 24-hour cough frequency (coughs per hour)
Timepoint [1] 0 0
Week 6
Secondary outcome [1] 0 0
Effect of NAL ER on the EXAcerbation of Chronic pulmonary disease Tool
Timepoint [1] 0 0
Week 6
Secondary outcome [2] 0 0
Safety and tolerability of NAL ER
Timepoint [2] 0 0
Screening through 14 day post last dose
Secondary outcome [3] 0 0
24-hour cough frequency (Coughs per hour)
Timepoint [3] 0 0
Weeks 2, 4, 6
Secondary outcome [4] 0 0
Awake cough frequency (Coughs per hour)
Timepoint [4] 0 0
Weeks 2, 4, 6
Secondary outcome [5] 0 0
Sleep cough frequency (Coughs per hour)
Timepoint [5] 0 0
Weeks 2, 4, 6
Secondary outcome [6] 0 0
EXACT© (EXAcerbation of Chronic pulmonary disease Tool) (EXAcerbation of Chronic pulmonary disease Tool)
Timepoint [6] 0 0
Weeks 1, 2, 3, 4, 5, 6
Secondary outcome [7] 0 0
CS-NRS (Cough Severity Numerical Rating Scale)
Timepoint [7] 0 0
Weeks 1, 2, 3, 4, 5, 6
Secondary outcome [8] 0 0
LCQ© (Leicester Cough Questionnaire)
Timepoint [8] 0 0
Week 6
Secondary outcome [9] 0 0
L-IPF© (Living with Pulmonary Fibrosis Impacts Questionnaire)
Timepoint [9] 0 0
Week 6
Secondary outcome [10] 0 0
L-IPF© (Living with Pulmonary Fibrosis Symptoms Questionnaire)
Timepoint [10] 0 0
Week 6
Secondary outcome [11] 0 0
EQ-5D-5L™
Timepoint [11] 0 0
Week 6
Secondary outcome [12] 0 0
PGI-S Cough (Patient Global Impression of Severity for Cough)
Timepoint [12] 0 0
Weeks 2, 4, 6
Secondary outcome [13] 0 0
PGI-S IPF (Patient Global Impression of Severity and Change for IPF)
Timepoint [13] 0 0
Weeks 2, 4, 6
Secondary outcome [14] 0 0
CGI-S, (Clinicians Global Impression of Severity)
Timepoint [14] 0 0
Baseline and Week 6
Secondary outcome [15] 0 0
PGI-C Cough; (Patient Global Impression of Change for Cough)
Timepoint [15] 0 0
Weeks 2, 4, 6
Secondary outcome [16] 0 0
PGI-C IPF (Patient Global Impression of Change in IPF symptoms)
Timepoint [16] 0 0
Weeks 2, 4, 6
Secondary outcome [17] 0 0
CGI-C
Timepoint [17] 0 0
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 subject's
ability to successfully complete the study.

- Pregnant or lactating female subject.

- 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.

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
Recruiting
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
14/10/2024
Actual
Sample size
Target
160
Accrual to date
Final
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
Ajax
Country [2] 0 0
Canada
State/province [2] 0 0
Vancouver
Country [3] 0 0
Chile
State/province [3] 0 0
Concepcion
Country [4] 0 0
Chile
State/province [4] 0 0
Quillota
Country [5] 0 0
Chile
State/province [5] 0 0
Santiago
Country [6] 0 0
Chile
State/province [6] 0 0
Talca
Country [7] 0 0
Chile
State/province [7] 0 0
Valparaiso
Country [8] 0 0
Chile
State/province [8] 0 0
Vina del Mar
Country [9] 0 0
Germany
State/province [9] 0 0
Essen
Country [10] 0 0
Germany
State/province [10] 0 0
Frankfurt am Main
Country [11] 0 0
Germany
State/province [11] 0 0
Hannover
Country [12] 0 0
Germany
State/province [12] 0 0
Leipzig
Country [13] 0 0
Germany
State/province [13] 0 0
Mainz
Country [14] 0 0
Germany
State/province [14] 0 0
Solingen
Country [15] 0 0
Italy
State/province [15] 0 0
Bologna
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
Milano
Country [19] 0 0
Italy
State/province [19] 0 0
Monza
Country [20] 0 0
Italy
State/province [20] 0 0
Napoli
Country [21] 0 0
Italy
State/province [21] 0 0
Padua
Country [22] 0 0
Italy
State/province [22] 0 0
Palermo
Country [23] 0 0
Italy
State/province [23] 0 0
Roma
Country [24] 0 0
Italy
State/province [24] 0 0
Rome
Country [25] 0 0
Netherlands
State/province [25] 0 0
's-Hertogenbosch
Country [26] 0 0
Netherlands
State/province [26] 0 0
Den Haag
Country [27] 0 0
Netherlands
State/province [27] 0 0
Groningen
Country [28] 0 0
Netherlands
State/province [28] 0 0
Rotterdam
Country [29] 0 0
Poland
State/province [29] 0 0
Gdansk
Country [30] 0 0
Poland
State/province [30] 0 0
Krakow
Country [31] 0 0
Poland
State/province [31] 0 0
Lodz
Country [32] 0 0
Poland
State/province [32] 0 0
Olsztyn
Country [33] 0 0
Poland
State/province [33] 0 0
Sosnowiec
Country [34] 0 0
Poland
State/province [34] 0 0
Szczecin
Country [35] 0 0
Spain
State/province [35] 0 0
Barcelona
Country [36] 0 0
Spain
State/province [36] 0 0
Madrid
Country [37] 0 0
Spain
State/province [37] 0 0
Santander
Country [38] 0 0
Turkey
State/province [38] 0 0
Ankara
Country [39] 0 0
Turkey
State/province [39] 0 0
Antalya
Country [40] 0 0
Turkey
State/province [40] 0 0
Canakkale
Country [41] 0 0
Turkey
State/province [41] 0 0
Istanbul
Country [42] 0 0
Turkey
State/province [42] 0 0
Izmir
Country [43] 0 0
Turkey
State/province [43] 0 0
Selcuklu
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Cambridge
Country [45] 0 0
United Kingdom
State/province [45] 0 0
Cottingham
Country [46] 0 0
United Kingdom
State/province [46] 0 0
Edinburgh
Country [47] 0 0
United Kingdom
State/province [47] 0 0
Londonderry
Country [48] 0 0
United Kingdom
State/province [48] 0 0
London
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Manchester
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Norwich
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Nottingham
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Oxford
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study of
nalbuphine ER (NAL ER).

After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1)
to one of four treatment arms.

- Arm 1: Placebo

- Arm 2: 27 mg nalbuphine ER

- Arm 3: 54 mg nalbuphine ER

- Arm 4: 108 mg nalbuphine ER

Each arm will be titrated to their fixed dose during the blinded 2-week Titration period
followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05964335
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Clark, MD
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
203-654-3284
Fax 0 0
Email 0 0
Beata.Dworakowska@trevitherapeutics.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05964335