Refractory Chronic Cough Improvement Via NAL ER (RIVER) (RIVER)
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| ClinicalTrials.gov Identifier: NCT05962151 |
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Recruitment Status :
Recruiting
First Posted : July 27, 2023
Last Update Posted : May 1, 2024
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Sponsor:
Trevi Therapeutics
Information provided by (Responsible Party):
Trevi Therapeutics
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Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Refractory Chronic Cough | Drug: Nalbuphine ER Drug: Placebo | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 60 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | November 30, 2023 |
| Estimated Primary Completion Date : | September 2024 |
| Estimated Study Completion Date : | October 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: NAL ER
NAL ER, tablets, 27 mg QD to BID, 54 mg BID, 108 mg BID
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Drug: Nalbuphine ER
Oral tablets
Other Name: Active |
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Placebo Comparator: Placebo
Placebo, tablets, 0 mg QD to BID, 0 mg BID, 0 mg BID
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Drug: Placebo
Oral tablets |
Primary Outcome Measures :
- 24 hr cough frequency [ Time Frame: Day 21 versus Baseline ]Relative change in frequency (coughs per hour) versus Placebo
Secondary Outcome Measures :
- Number of participants with treatment related adverse events, as assessed by CTCAE v.5.0 [ Time Frame: Baseline through follow-up ]Adverse events, clinical labs, vital signs, physical exams, electrocardiograms
- Subjective Opiate Withdrawal Scale [ Time Frame: Daily for 14 days after last dose in Period 2 ]16 item questionnaire for 14 days following last dose of study drug
- 24 hour cough frequency [ Time Frame: Days 7 and 14 versus Baseline ]Relative change in frequency (coughs per hour) versus Placebo
- 24 hour cough frequency [ Time Frame: Days 7, 14, and 21 versus Baseline ]Proportion of responders with >=30%, 50% and 75% reduction in frequency versus Placebo
- Awake cough frequency [ Time Frame: Days 7, 14, and 21 versus Baseline ]Relative change in frequency (coughs per hour) versus Placebo
- Sleep cough frequency [ Time Frame: Days 7, 14, and 21 versus Baseline ]Relative change in frequency (coughs per hour) versus Placebo
- Cough Severity Visual Analogue Scale [ Time Frame: Days 7, 14, and 21 versus Baseline ]1 item scale with minimum score of 0 (no cough) to 10 (worst cough) versus Placebo
- Leicester Cough Questionnaire [ Time Frame: Day 21 versus Baseline ]19 item questionnaire with a grading of 1 (all the time ) to 7 (none of the time) versus Placebo
- Patient-Reported Cough Frequency (change) [ Time Frame: Days 7, 14, and 21 versus Baseline ]Change versus Placebo
- Patient-Reported Cough Frequency (proportion) [ Time Frame: Days 7, 14, and 21 versus Baseline ]Proportion of responders with improvement in at least one category versus Placebo
- Patient Global Impression of Cough Severity [ Time Frame: Days 7, 14, and 21 versus Baseline ]1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
- Patient Global Impression of Cough Change [ Time Frame: Days 7, 14, and 21 versus Baseline ]1 item question with a 7 point grading from "much better to much worse" versus Placebo
- Clinicians Global Impression of Cough Severity [ Time Frame: Day 21 versus Baseline (both treatment periods) ]1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
- Clinicians Global Impression of Cough Change [ Time Frame: Day 21 versus Baseline (both treatment periods) ]1 item question with a 7 point grading from "very much improved to very much worse" versus Placebo
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05962151
Contacts
| Contact: Sherry Minor | 203-684-1308 | Sherry.Minor@trevitherapeutics.com | |
| Contact: Connie Crum, RN | 203-599-0265 | Connie.Crum@trevitherapeutics.com |
Locations
| Canada, Ontario | |
| McMaster University Medical Centre | Recruiting |
| Hamilton, Ontario, Canada, L8N 3Z5 | |
| Contact: Imran Satia 905-521-2100 ext 76228 satiai@mcmaster.ca | |
| Inspiration Research | Recruiting |
| Toronto, Ontario, Canada, M5T 3A9 | |
| Contact: Kayla Johnston 416-944-9602 kjohnston@inspirationresearch.ca | |
| Canada, Quebec | |
| CIC Mauricie Inc. | Recruiting |
| Trois-Rivières, Quebec, Canada, G8T 7A1 | |
| Contact: Sonia Groleau 819-373-1128 ext 5 groleau@cic-mauricie.ca | |
| United Kingdom | |
| Hull and East Yorkshire Hospitals NHS Trust - Castle Hill Hospital | Recruiting |
| Cottingham, East Riding Of Yorkshire, United Kingdom, HU16 5JQ | |
| Contact: Caroline Wright 1482624067 C.Wright@hull.ac.uk | |
| Kings College Hospital NHS Foundation Trust | Recruiting |
| London, Greater London, United Kingdom, SE5 9RS | |
| Contact: Katie Rhatigan +44 2032991096 k.rhatigan@nhs.net | |
| University Hospital of South Manchester NHS Foundation Trust (UHSM) - Wythenshawe Hospital | Recruiting |
| Manchester, Greater Manchester, United Kingdom, M23 9LT | |
| Contact: Swapnika Putla 1612915031 Swapnika.Putla@mft.nhs.uk | |
| Accellacare South London | Recruiting |
| Sidcup, Kent, United Kingdom, DA14 6LT | |
| Contact: Nowshin Rahman 02033 013 000 nowshin.rahman@accellacare.com | |
| Accellacare North London | Recruiting |
| Northwood, Middlesex, United Kingdom, HA6 2RN | |
| Contact: Charlotte Savill 01923 742 400 charlotte.savill@accellacare.com | |
| Accellacare Northamptonshire | Recruiting |
| Corby, Northamptonshire, United Kingdom, NN18 9EZ | |
| Contact: June Jacob june.jacob@accellacare.com | |
| Belfast City Hospital | Recruiting |
| Belfast, Northern Ireland, United Kingdom, BT9 7AB | |
| Contact: Danielle Dawson 02895048253 danielle.dawson@belfasttrust.hscni.net | |
| North Tyneside General Hospital - Northumbria Healthcare NHS Foundation Trust | Recruiting |
| North Shields, Tynemouth, United Kingdom, NE29 8NH | |
| Contact: Jane Luke 8448118111 jane.luke@northumbria-healthcare.nhs.uk | |
| Accellacare Warwickshire | Recruiting |
| Coventry, Warwickshire, United Kingdom, CV3 4FJ | |
| Contact: Jackie Smith +44 (0) 1926290289 Jackie.Smith@accellacare.com | |
| University Hospitals Birmingham NHS Foundation Trust | Recruiting |
| Birmingham, West Midlands, United Kingdom, B9 5SS | |
| Contact: Emma Bruce emma.bruce@uhb.nhs.uk | |
| Accellacare Yorkshire | Recruiting |
| Shipley, Yorkshire, United Kingdom, BD18 3SA | |
| Contact: Amy Rosie Amy.rosie@accellacare.com | |
Sponsors and Collaborators
Trevi Therapeutics
Investigators
| Study Director: | David Clark, MD | Trevi Therapeutics |
| Responsible Party: | Trevi Therapeutics |
| ClinicalTrials.gov Identifier: | NCT05962151 |
| Other Study ID Numbers: |
NAL04-201 |
| First Posted: | July 27, 2023 Key Record Dates |
| Last Update Posted: | May 1, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by Trevi Therapeutics:
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RCC Cough Nalbuphine |
Additional relevant MeSH terms:
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Cough Chronic Cough Respiration Disorders Respiratory Tract Diseases Signs and Symptoms, Respiratory Nalbuphine Analgesics, Opioid |
Narcotics Central Nervous System Depressants Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents |