Clinical trial NCT05964335: Cough Reduction in IPF with Nalbuphine ER
Official 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Cough
Nalbuphine
Lead sponsor: Trevi Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 with placebo and increasing doses of 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.

For more information see the country specific approved websites:

Germany, Netherlands, Poland, Spain, Italy, Chile: TheCoralTrial.com United Kingdom, Australia, Canada: CoralCoughTrial.com Turkey: please refer to the list of locations and reach out to the site directly

Detailed description: This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study.

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 according to Table: Dosing Scheme, followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.

Subjects will be taken off study drug at the end of the Fixed Dose Period and followed off treatment for an additional 2 weeks.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Effect of NAL ER on 24-hour cough frequency (coughs per hour)
timeFrame: Week 6
Secondary outcomes:
measure: Effect of NAL ER on the EXAcerbation of Chronic pulmonary disease Tool
timeFrame: Week 6
measure: Safety and tolerability of NAL ER
timeFrame: Screening through 14 day post last dose
measure: 24-hour cough frequency (Coughs per hour)
timeFrame: Weeks 2, 4, 6
measure: Awake cough frequency (Coughs per hour)
timeFrame: Weeks 2, 4, 6
measure: Sleep cough frequency (Coughs per hour)
timeFrame: Weeks 2, 4, 6
measure: EXACT© (EXAcerbation of Chronic pulmonary disease Tool) (EXAcerbation of Chronic pulmonary disease Tool)
timeFrame: Weeks 1, 2, 3, 4, 5, 6
measure: CS-NRS (Cough Severity Numerical Rating Scale)
timeFrame: Weeks 1, 2, 3, 4, 5, 6
measure: LCQ© (Leicester Cough Questionnaire)
timeFrame: Week 6
measure: L-IPF© (Living with Pulmonary Fibrosis Impacts Questionnaire)
timeFrame: Week 6
measure: L-IPF© (Living with Pulmonary Fibrosis Symptoms Questionnaire)
timeFrame: Week 6
measure: EQ-5D-5L™
timeFrame: Week 6
measure: PGI-S Cough (Patient Global Impression of Severity for Cough)
timeFrame: Weeks 2, 4, 6
measure: PGI-S IPF (Patient Global Impression of Severity and Change for IPF)
timeFrame: Weeks 2, 4, 6
measure: CGI-S, (Clinicians Global Impression of Severity)
timeFrame: Baseline and Week 6
measure: PGI-C Cough; (Patient Global Impression of Change for Cough)
timeFrame: Weeks 2, 4, 6
measure: PGI-C IPF (Patient Global Impression of Change in IPF symptoms)
timeFrame: Weeks 2, 4, 6
measure: CGI-C
timeFrame: Week 6
Other outcomes:
Locations:
city: Box Hill
country: Australia
facility: Eastern Health-Box Hill Hospital
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Kent Town
country: Australia
facility: Respiratory Clinical Trials Pty Ltd
city: Spearwood
country: Australia
facility: TrialsWest Pty Ltd
city: Westmead
country: Australia
facility: Westmead Hospital
city: Trois-Rivieres
country: Canada
facility: CIC Mauricie Inc.
state: Quebec
city: Ajax
country: Canada
facility: Dynamic Drug Advancement
city: Vancouver
country: Canada
facility: Centre for Lung Health Clinic
city: Vancouver
country: Canada
facility: The Pacific Lung Health Centre - St. Pauls Hospital
city: Concepcion
country: Chile
facility: Hospital Clinico Regional Dr. Guillermo Grant Benavente
city: Quillota
country: Chile
facility: Centro de Investigaciones Medicas Cemedin Ltda.
city: Santiago
country: Chile
facility: Clinica Universidad de los Andes
city: Talca
country: Chile
facility: Centro de Investigacion del Maule
city: Valparaiso
country: Chile
facility: Hospital Carlos Van Buren
city: Vina del Mar
country: Chile
facility: Oncocentro APYS
city: Essen
country: Germany
facility: Universitatsklinik Ruhrlandklinik, Westdeutsches Lungenzentrum
city: Frankfurt am Main
country: Germany
facility: IKF Institut fuer klinische Forschung Frankfurt
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Hannover Medical School
city: Leipzig
country: Germany
facility: University Hospital of Leipzig
city: Mainz
country: Germany
facility: University Medical Center of Johannes Gutenberg-University Mainz
city: Mainz
country: Germany
facility: IKF Pneumologie Mainz, Helix Medical Excellence Center Mainz
city: Solingen
country: Germany
facility: Krankenhaus Bethanien
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele- Ospedale Gaspare Rodolico
city: Foggia
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Di Foggia
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
city: Padua
country: Italy
facility: Azienda Ospedaliera di Padova
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Den Haag
country: Netherlands
facility: HMC (Haaglanden Medisch Centrum) Bronovo
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum 1
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne (UCK)
city: Krakow
country: Poland
facility: Niepubliczny Zaklad Opieki Zdrowotnej Centrum Medyczne ProMiMed sp z o.o., sp.k.
city: Lodz
country: Poland
facility: Uniwersytecki Szpital Kliniczny nr 1 im. N. Barlickiego
city: Olsztyn
country: Poland
facility: Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Wojewodzki Szpital Zespolony w Szczecinie
city: Barcelona
country: Spain
facility: Clinica Mi Tres Torres Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Madrid
country: Spain
facility: Hospital La Milagrosa
city: Santander
country: Spain
facility: HUMV
city: Ankara
country: Turkey
facility: Gulhane Askeri Tip Akademisi (GATA) - Gulhane Askeri Tip Fakultesi (Gulhane Military Medical Academy and Medical School)
city: Antalya
country: Turkey
facility: Akdeniz University Faculty of Medicine
city: Canakkale
country: Turkey
facility: Canakkale Onsekiz Mart Universitesi (COMU) - Tip Fakultesi Hastanesi
city: Istanbul
country: Turkey
facility: Sureyyapasa Gogus Hastaliklari ve Gogus Cerrahisi Egitim ve Arastirma Hastanesi
city: Izmir
country: Turkey
facility: Ege University Medical Faculty
city: Selcuklu
country: Turkey
facility: Selcuk Universty Medical Faculty
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
city: Cottingham
country: United Kingdom
facility: Hull and East Yorkshire - Castle Hill Hospital
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary Of Edinburgh
city: Londonderry
country: United Kingdom
facility: Altnagelvin Area Hospital
city: London
country: United Kingdom
facility: University College London
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Oxford
country: United Kingdom
facility: Churchill Hospital
city: Portadown
country: United Kingdom
facility: Southern Health & Social Care Trust, Craigavon Area Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Trevi Therapeutics
name: Chief Development Officer
role: STUDY_DIRECTOR
References: