Refractory Chronic Cough Improvement Via NAL ER (RIVER)
- Registration Number
- NCT05962151
- Lead Sponsor
- Trevi Therapeutics
- Brief Summary
The main purpose of this study is to evaluate the effect of NAL ER on 24-hour cough frequency and to assess safety and tolerability of NAL-ER for treatment of refractory chronic cough.
- Detailed Description
A double-blind, randomized, placebo-controlled, 2-period crossover study for the treatment of cough with NAL ER in subjects with Refractory Chronic Cough.
Based on the screening cough monitor results, the study will enroll subjects in a 1:1 ratio to subgroups of 10-19 coughs/hour and ≥20 coughs/hour.
After meeting eligibility during the screening period, subjects will be randomly assigned to one of the following sequences:
* NAL ER in Treatment Period 1, followed by Placebo (PBO) in Treatment Period 2 OR
* PBO in Treatment Period 1, followed by NAL ER in Treatment Period 2.
Each treatment period lasts 21 days and are separated by a 21-day washout period. Subjects on NAL ER will have the dose titrated from 27 mg once a day (QD) to 108 mg twice a day (BID).
Study visits in each treatment period will be at Day -1 for Baseline cough assessments, and at Days 6, 13, and 20. Subjects will have blood drawn for pharmacokinetic (PK) analysis of nalbuphine plasma concentration. Subjects will also complete questionnaires for efficacy evaluations and undergo safety evaluations including an electrocardiogram (ECG).
At the Screening and Baseline visits and on Days 6, 13, and 20 during each treatment period, site staff will place an electronic cough monitor on the subject, which will be worn for a 24-hour recording period to assess cough frequency. At the end of each recording session (Days 7, 14, and 21), the monitor will be removed at home by the subject, and the subjects will complete Patient Reported Outcomes (PROs) questionnaires in the electronic diary.
Subjects will be taken off study drug at the end of Treatment Period 2 and followed off treatment for an additional 2 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 66
- Diagnosis of refractory chronic cough (RCC) for at least one year
- Chest radiograph or CT of thorax within 24 months or during screening not demonstrating any significant abnormalities contributing to RCC
- Diagnosis of sleep apnea
- Respiratory tract infection within 6 weeks of Baseline
- History of bronchiectasis, COPD, or IPF
- History of uncontrolled asthma
- Current smokers/vapers, quit smoking with <=12 months, using nicotine supplements, or history of >=20 pack years
- History of major psychiatric disorder
- History of substance abuse
- Pregnant or lactating females
- Known intolerance to opioids
- Abnormal kidney or liver functions based on Screening lab results.
- Known hypersensitivity to nalbuphine or to NAL ER excipients
- Previous participation in a nalbuphine ER clinical study
- Use of opiates, benzodiazepines, or MAOIs within 14 days of Baseline
- Use of pregabalin, gabapentin, thalidomide for treatment of cough within 14 days of Baseline
- Use of ACE inhibitors within 12 weeks of Baseline
- 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.
- Use of unstable doses of cough suppressants within 14 days of Baseline
- Use of unstable doses of medications that affect serotonergic neurotransmission that may cause serotonin syndrome with opioids within14 days of Baseline
- Use of unstable doses of P450 isozyme inhibitors/inducers within 14 days of Baseline
Other protocol defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description First NAL ER, then Placebo NAL ER Participants will receive NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 1, followed by placebo matched to NAL ER in Treatment Period 2. First NAL ER, then Placebo Placebo Participants will receive NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 1, followed by placebo matched to NAL ER in Treatment Period 2. First Placebo then NAL ER Placebo Participants will receive placebo matched to NAL ER in Treatment Period 1, followed by NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 2. First Placebo then NAL ER NAL ER Participants will receive placebo matched to NAL ER in Treatment Period 1, followed by NAL ER at escalating doses (27 mg QD to BID, 54 mg BID, and 108 mg BID) in Treatment Period 2.
- Primary Outcome Measures
Name Time Method Relative Change From Baseline in 24-hour Cough Frequency at Day 21 Baseline, Day 21
- Secondary Outcome Measures
Name Time Method Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) Up to Week 15 Relative Change From Baseline in 24-hour Cough Frequency at Days 7 and 14 Baseline, Day 7 and 14 Percentage of Participants With >=30%, 50% and 75% Reduction in 24-hour Cough Frequency at Days 7, 14, and 21 At Days 7, 14, and 21 Relative Change From Baseline in Awake Cough Frequency at Days 7, 14, and 21 Baseline, Day 7, 14 and 21 Relative Change From Baseline in Sleep Cough Frequency at Days 7, 14, and 21 Baseline, Day 7, 14 and 21 Change From Baseline in Cough Severity Visual Analogue Scale at Days 7, 14, and 21 Baseline, Day 7, 14 and 21 Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Day 21 Baseline, Day 21 Change From Baseline in Patient-Reported Cough Frequency (PR-CF) at Days 7, 14, and 21 Baseline, Day 7, 14 and 21 Percentage of PR-CF Responders With at Least one Category Improvement at Days 7, 14, and 21 At Days 7, 14, and 21 Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough at Days 7, 14, and 21 Baseline, Day 7, 14 and 21 Absolute Values of Patient Global Impression of Change for Cough (PGI-C) Score at Days 7, 14, and 21 At Days 7, 14, and 21 Change From Baseline in Clinicians Global Impression of Cough Severity Score at Day 21 Baseline, Day 21 Absolute Values of Clinicians Global Impression of Change for Cough Score at Day 21 At Day 21
Trial Locations
- Locations (14)
Egin Research Ltd
🇬🇧High Wycombe, United Kingdom
North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust
🇬🇧North Shields, Tynemouth, United Kingdom
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada
CIC Mauricie Inc.
🇨🇦Trois-Rivières, Quebec, Canada
Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
🇬🇧Cottingham, East Riding Of Yorkshire, United Kingdom
Kings College Hospital NHS Foundation Trust
🇬🇧London, Greater London, United Kingdom
University Hospital of South Manchester NHS Foundation Trust (UHSM) - Wythenshawe Hospital
🇬🇧Manchester, Greater Manchester, United Kingdom
Accellacare South London
🇬🇧Orpington, Kent, United Kingdom
Inspiration Research
🇨🇦Toronto, Ontario, Canada
Accellacare North London
🇬🇧Northwood, Middlesex, United Kingdom
Belfast City Hospital
🇬🇧Belfast, Northern Ireland, United Kingdom
Accellacare Warwickshire
🇬🇧Coventry, Warwickshire, United Kingdom
University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, West Midlands, United Kingdom
Accellacare Yorkshire
🇬🇧Shipley, Yorkshire, United Kingdom