Clinical trial NCT05962151: Refractory Chronic Cough Improvement Via NAL ER (RIVER)
Official title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Two-Period Crossover Efficacy and Safety Study of Nalbuphine ER Tablets for the Treatment of Refractory Chronic Cough
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Refractory Chronic Cough
Keywords: RCC
Cough
Nalbuphine
Lead sponsor: Trevi Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-27
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Key Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Relative Change From Baseline in 24-hour Cough Frequency at Day 21
timeFrame: Baseline, Day 21
Secondary outcomes:
measure: Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 15
measure: Relative Change From Baseline in 24-hour Cough Frequency at Days 7 and 14
timeFrame: Baseline, Day 7 and 14
measure: Percentage of Participants With >=30%, 50% and 75% Reduction in 24-hour Cough Frequency at Days 7, 14, and 21
timeFrame: At Days 7, 14, and 21
measure: Relative Change From Baseline in Awake Cough Frequency at Days 7, 14, and 21
timeFrame: Baseline, Day 7, 14 and 21
measure: Relative Change From Baseline in Sleep Cough Frequency at Days 7, 14, and 21
timeFrame: Baseline, Day 7, 14 and 21
measure: Change From Baseline in Cough Severity Visual Analogue Scale at Days 7, 14, and 21
timeFrame: Baseline, Day 7, 14 and 21
measure: Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score at Day 21
timeFrame: Baseline, Day 21
measure: Change From Baseline in Patient-Reported Cough Frequency (PR-CF) at Days 7, 14, and 21
timeFrame: Baseline, Day 7, 14 and 21
measure: Percentage of PR-CF Responders With at Least one Category Improvement at Days 7, 14, and 21
timeFrame: At Days 7, 14, and 21
measure: Change From Baseline in Patient Global Impression of Severity (PGI-S) Cough at Days 7, 14, and 21
timeFrame: Baseline, Day 7, 14 and 21
measure: Absolute Values of Patient Global Impression of Change for Cough (PGI-C) Score at Days 7, 14, and 21
timeFrame: At Days 7, 14, and 21
measure: Change From Baseline in Clinicians Global Impression of Cough Severity Score at Day 21
timeFrame: Baseline, Day 21
measure: Absolute Values of Clinicians Global Impression of Change for Cough Score at Day 21
timeFrame: At Day 21
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Inspiration Research
state: Ontario
city: Trois-Rivières
country: Canada
facility: CIC Mauricie Inc.
state: Quebec
city: Cottingham
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital
state: East Riding Of Yorkshire
city: London
country: United Kingdom
facility: Kings College Hospital NHS Foundation Trust
state: Greater London
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust (UHSM) - Wythenshawe Hospital
state: Greater Manchester
city: Orpington
country: United Kingdom
facility: Accellacare South London
state: Kent
city: Northwood
country: United Kingdom
facility: Accellacare North London
state: Middlesex
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
state: Northern Ireland
city: North Shields
country: United Kingdom
facility: North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust
state: Tynemouth
city: Coventry
country: United Kingdom
facility: Accellacare Warwickshire
state: Warwickshire
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
state: West Midlands
city: Shipley
country: United Kingdom
facility: Accellacare Yorkshire
state: Yorkshire
city: High Wycombe
country: United Kingdom
facility: Egin Research Ltd
Study officials:
affiliation: Trevi Therapeutics
name: Chief Development Officer
role: STUDY_DIRECTOR
References: