Refractory Chronic Cough Improvement Via NAL ER (RIVER)

NCT05962151 | Completed Phase 2 Results FDA Drug

• 1 other identifier: NAL04-201
• Study Type: interventional
• Target: 66
• Locations: 2 countries
• Sites: 14

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.

Conditions

Refractory Chronic Cough

Keywords

RCC; Cough; Nalbuphine

Outcome Measures

Primary Outcomes (1)

• Relative Change From Baseline in 24-hour Cough Frequency at Day 21

  Relative change in 24-hour (combined daytime and nighttime) cough frequency (coughs per hour) from baseline was assessed. Assessment was done using objective digital cough monitoring. Baseline was defined as the last non-missing assessment, prior to the first dose of study drug.

  Baseline, Day 21

Secondary Outcomes (17)

• Number of Participants Who Experienced at Least One Treatment Emergent Adverse Events (TEAEs)

  Up to Week 15

• Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments

  Up to Week 15

• Number of Participants With Clinically Significant Changes in Vital Sign Parameters

  Up to Week 15

• Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)

  Up to Week 15

• Number of Participants With Clinically Significant Changes in Physical Examination Parameters

  Up to Week 15

Study Arms (2)

First NAL ER, then Placebo

EXPERIMENTAL

Participants received 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.

Drug: NAL ER; Drug: Placebo

First Placebo then NAL ER

EXPERIMENTAL

Participants received 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.

Drug: NAL ER; Drug: Placebo

Interventions

NAL ER DRUG

Oral tablets

Also known as: Nalbuphine

First NAL ER, then Placebo; First Placebo then NAL ER

Placebo DRUG

Oral tablets

First NAL ER, then Placebo; First Placebo then NAL ER

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Trevi Therapeutics: lead

Study Sites (14)

McMaster University Medical Centre

Hamilton, Ontario, L8N 3Z5, Canada

Location

Inspiration Research

Toronto, Ontario, M5T 3A9, Canada

Location

CIC Mauricie Inc.

Trois-Rivières, Quebec, G8T 7A1, Canada

Location

Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital

Cottingham, East Riding Of Yorkshire, HU16 5JQ, United Kingdom

Location

Kings College Hospital NHS Foundation Trust

London, Greater London, SE5 9RS, United Kingdom

Location

University Hospital of South Manchester NHS Foundation Trust (UHSM) - Wythenshawe Hospital

Manchester, Greater Manchester, M23 9LT, United Kingdom

Location

Accellacare South London

Orpington, Kent, BR5 3QG, United Kingdom

Location

Accellacare North London

Northwood, Middlesex, HA6 2RN, United Kingdom

Location

Belfast City Hospital

Belfast, Northern Ireland, BT9 7AB, United Kingdom

Location

North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust

North Shields, Tynemouth, NE29 8NH, United Kingdom

Location

Accellacare Warwickshire

Coventry, Warwickshire, CV3 4FJ, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2GW, United Kingdom

Location

Accellacare Yorkshire

Shipley, Yorkshire, BD18 3SA, United Kingdom

Location

Egin Research Ltd

High Wycombe, HP11 2QW, United Kingdom

Location

MeSH Terms

Conditions

Chronic Cough; Cough

Interventions

Nalbuphine

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: James Cassella, Ph.D, Chief Development Officer
• Organization: Trevi Therapeutics, Inc.

info@trevitherapeutics.com

203-304-2499

Study Officials

• Chief Development Officer

  Trevi Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: July 27, 2023
• Study Start: November 30, 2023
• Primary Completion: January 6, 2025
• Study Completion: January 6, 2025
• Last Updated: March 30, 2026
• Results First Posted: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); GB (11)