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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05962151
Other study ID # NAL04-201
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date November 30, 2023
Est. completion date October 2024

Study information

Verified date April 2024
Source Trevi Therapeutics
Contact Sherry Minor
Phone 203-684-1308
Email Sherry.Minor@trevitherapeutics.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

A 2-period crossover study for the treatment of cough in patients with Refractory Chronic Cough via Nalbuphine ER (NAL ER). Each period will last 21 days and are separated by 21 days. Subjects will be randomized in Treatment Period 1 to either NAL ER or matching placebo and evaluated for 21 days. After completion of the first phase, subjects who received NAL ER will crossover to placebo and subjects who received placebo will crossover to NAL ER to complete Treatment Period 2.


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 information / eligibility

Status Recruiting
Enrollment 60
Est. completion date October 2024
Est. primary completion date September 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Nalbuphine ER
Oral tablets
Placebo
Oral tablets

Locations

Country Name City State
Canada McMaster University Medical Centre Hamilton Ontario
Canada Inspiration Research Toronto Ontario
Canada CIC Mauricie Inc. Trois-Rivières Quebec
United Kingdom Belfast City Hospital Belfast Northern Ireland
United Kingdom University Hospitals Birmingham NHS Foundation Trust Birmingham West Midlands
United Kingdom Accellacare Northamptonshire Corby Northamptonshire
United Kingdom Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital Cottingham East Riding Of Yorkshire
United Kingdom Accellacare Warwickshire Coventry Warwickshire
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 North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust North Shields Tynemouth
United Kingdom Accellacare North London Northwood Middlesex
United Kingdom Accellacare Yorkshire Shipley Yorkshire
United Kingdom Accellacare South London Sidcup Kent

Sponsors (1)

Lead Sponsor Collaborator
Trevi Therapeutics

Countries where clinical trial is conducted

Canada,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 24 hr cough frequency Relative change in frequency (coughs per hour) versus Placebo Day 21 versus Baseline
Secondary Number of participants with treatment related adverse events, as assessed by CTCAE v.5.0 Adverse events, clinical labs, vital signs, physical exams, electrocardiograms Baseline through follow-up
Secondary Subjective Opiate Withdrawal Scale 16 item questionnaire for 14 days following last dose of study drug Daily for 14 days after last dose in Period 2
Secondary 24 hour cough frequency Relative change in frequency (coughs per hour) versus Placebo Days 7 and 14 versus Baseline
Secondary 24 hour cough frequency Proportion of responders with >=30%, 50% and 75% reduction in frequency versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Awake cough frequency Relative change in frequency (coughs per hour) versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Sleep cough frequency Relative change in frequency (coughs per hour) versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Cough Severity Visual Analogue Scale 1 item scale with minimum score of 0 (no cough) to 10 (worst cough) versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Leicester Cough Questionnaire 19 item questionnaire with a grading of 1 (all the time ) to 7 (none of the time) versus Placebo Day 21 versus Baseline
Secondary Patient-Reported Cough Frequency (change) Change versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Patient-Reported Cough Frequency (proportion) Proportion of responders with improvement in at least one category versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Patient Global Impression of Cough Severity 1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Patient Global Impression of Cough Change 1 item question with a 7 point grading from "much better to much worse" versus Placebo Days 7, 14, and 21 versus Baseline
Secondary Clinicians Global Impression of Cough Severity 1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo Day 21 versus Baseline (both treatment periods)
Secondary Clinicians Global Impression of Cough Change 1 item question with a 7 point grading from "very much improved to very much worse" versus Placebo Day 21 versus Baseline (both treatment periods)
See also
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