Cough Reduction in IPF With Nalbuphine ER
- Registration Number
- NCT05964335
- Lead Sponsor
- Trevi Therapeutics
- Brief Summary
The main purpose of the study is to evaluate the effect of NAL ER on 24-hour cough frequency using objective digital cough monitoring and to assess safety and tolerability of NAL ER.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 165
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 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description NAL ER 27 mg NAL ER BID NAL ER 54 mg NAL ER BID NAL ER 108 mg NAL ER BID Placebo Placebo Placebo, BID
- Primary Outcome Measures
Name Time Method Relative Change From Baseline in 24-hour Cough Frequency at Week 6 Baseline, Week 6
- Secondary Outcome Measures
Name Time Method 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 At Weeks 2, 4, and 6 Percentage of Responders With ≥30%, ≥50% and ≥75% Reduction in the 24-Hour Cough Frequency at Week 2, 4, and 6 At Weeks 2, 4, and 6 Relative Change From Baseline in Awake Cough Frequency at Week 2, 4, and 6 Baseline, Weeks 2, 4, and 6 Change From Baseline in Clinicians Global Impression of Severity (CGI-S) score at Week 6 Baseline, Week 6 Absolute Values for CGI-C IPF Score at Week 6 At Week 6 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 At Week 6 Change From Baseline in Evaluating Respiratory Symptoms in Idiopathic Pulmonary Fibrosis (E-RS:IPF) Cough subscale at Week 6 Baseline, Week 6 Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) Up to Week 12 Relative Change From Baseline in 24-hour Cough Frequency at Weeks 2,4, and 6 Baseline, Weeks 2, 4, and 6 Relative Change From Baseline in Sleep Cough Frequency at Week 2, 4, and 6 Baseline, Weeks 2, 4, and 6 Change From Baseline in E-RS: IPF Cough Subscale at Weeks 1, 2, 3, 4, 5, and 6 Baseline, Weeks 1, 2, 3, 4, 5, 6 Percentage of E-RS: IPF Cough Subscale Responders With At least one Category Improvement at Weeks 1, 2, 3, 4, 5, and 6 At Weeks 1, 2, 3, 4, 5, and 6 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 Baseline, Weeks 1, 2, 3, 4, 5, and 6 Change From Baseline in Cough Severity Numerical Rating Scale (CS-NRS) at Weeks 1, 2, 3, 4, 5, and 6 Baseline, Weeks 1, 2, 3, 4, 5, and 6 Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Week 6 Baseline, Week 6 Percentage of LCQ Total Score Responders With 1.3-Point Increase Response at Week 6 At Week 6 Change From Baseline in LCQ Domains and Individual Items at Week 6 Baseline, Week 6 Change From Baseline in Living With Pulmonary Fibrosis Impacts Questionnaire (L-IPF©) at Week 6 Baseline, Week 6 Change From Baseline in Living With Pulmonary Fibrosis Symptoms Questionnaire (L-IPF) and its Domains at Week 6 Baseline, Week 6 Change from Baseline in EuroQol 5-Dimension 5-Level (EQ-5D-5L™) at Week 6 Baseline, Week 6 Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough at Weeks 2, 4, and 6 Baseline, Weeks 2, 4, and 6 Absolute Values of PGI-C Cough Score at Weeks 2, 4, and 6 At Weeks 2, 4, and 6 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 At Weeks 2, 4, and 6 Change from Baseline in PGI-S IPF at Weeks 2, 4, and 6 Baseline, Weeks 2, 4, and 6 Absolute Values of PGI-C IPF at Weeks 2, 4, and 6 At Weeks 2, 4, and 6
Trial Locations
- Locations (59)
Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Eastern Health-Box Hill Hospital
🇦🇺Box Hill, Australia
Concord Repatriation General Hospital
🇦🇺Concord, Australia
Austin Hospital
🇦🇺Heidelberg, Australia
Respiratory Clinical Trials Pty Ltd
🇦🇺Kent Town, Australia
TrialsWest Pty Ltd
🇦🇺Spearwood, Australia
Westmead Hospital
🇦🇺Westmead, Australia
CIC Mauricie Inc.
🇨🇦Trois-Rivieres, Quebec, Canada
Dynamic Drug Advancement
🇨🇦Ajax, Canada
Centre for Lung Health Clinic
🇨🇦Vancouver, Canada
Scroll for more (49 remaining)Queen Elizabeth Hospital Birmingham - University Hospitals Birmingham NHS Foundation Trust🇬🇧Birmingham, United Kingdom