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Refractory Chronic Cough Improvement Via NAL ER (RIVER) (RIVER)

Primary Purpose

Refractory Chronic Cough

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Nalbuphine ER
Placebo
Sponsored by
Trevi Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Chronic Cough focused on measuring RCC, Cough, Nalbuphine

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    NAL ER

    Placebo

    Arm Description

    NAL ER, tablets, 27 mg QD to BID, 54 mg BID, 108 mg BID

    Placebo, tablets, 0 mg QD to BID, 0 mg BID, 0 mg BID

    Outcomes

    Primary Outcome Measures

    24 hr cough frequency
    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
    Adverse events, clinical labs, vital signs, physical exams, electrocardiograms
    Subjective Opiate Withdrawal Scale
    16 item questionnaire for 14 days following last dose of study drug
    24 hour cough frequency
    Relative change in frequency (coughs per hour) versus Placebo
    24 hour cough frequency
    Proportion of responders with >=30%, 50% and 75% reduction in frequency versus Placebo
    Awake cough frequency
    Relative change in frequency (coughs per hour) versus Placebo
    Sleep cough frequency
    Relative change in frequency (coughs per hour) versus Placebo
    Cough Severity Visual Analogue Scale
    1 item scale with minimum score of 0 (no cough) to 10 (worst cough) versus Placebo
    Leicester Cough Questionnaire
    19 item questionnaire with a grading of 1 (all the time ) to 7 (none of the time) versus Placebo
    Patient-Reported Cough Frequency (change)
    Change versus Placebo
    Patient-Reported Cough Frequency (proportion)
    Proportion of responders with improvement in at least one category versus Placebo
    Patient Global Impression of Cough Severity
    1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
    Patient Global Impression of Cough Change
    1 item question with a 7 point grading from "much better to much worse" versus Placebo
    Clinicians Global Impression of Cough Severity
    1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
    Clinicians Global Impression of Cough Change
    1 item question with a 7 point grading from "very much improved to very much worse" versus Placebo

    Full Information

    First Posted
    July 7, 2023
    Last Updated
    August 14, 2023
    Sponsor
    Trevi Therapeutics
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05962151
    Brief Title
    Refractory Chronic Cough Improvement Via NAL ER (RIVER)
    Acronym
    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

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    September 2023 (Anticipated)
    Primary Completion Date
    September 2024 (Anticipated)
    Study Completion Date
    October 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Trevi Therapeutics

    4. Oversight

    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
    Data Monitoring Committee
    No

    5. Study Description

    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Refractory Chronic Cough
    Keywords
    RCC, Cough, Nalbuphine

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Crossover Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    60 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    NAL ER
    Arm Type
    Experimental
    Arm Description
    NAL ER, tablets, 27 mg QD to BID, 54 mg BID, 108 mg BID
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo, tablets, 0 mg QD to BID, 0 mg BID, 0 mg BID
    Intervention Type
    Drug
    Intervention Name(s)
    Nalbuphine ER
    Other Intervention Name(s)
    Active
    Intervention Description
    Oral tablets
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Oral tablets
    Primary Outcome Measure Information:
    Title
    24 hr cough frequency
    Description
    Relative change in frequency (coughs per hour) versus Placebo
    Time Frame
    Day 21 versus Baseline
    Secondary Outcome Measure Information:
    Title
    Number of participants with treatment related adverse events, as assessed by CTCAE v.5.0
    Description
    Adverse events, clinical labs, vital signs, physical exams, electrocardiograms
    Time Frame
    Baseline through follow-up
    Title
    Subjective Opiate Withdrawal Scale
    Description
    16 item questionnaire for 14 days following last dose of study drug
    Time Frame
    Daily for 14 days after last dose in Period 2
    Title
    24 hour cough frequency
    Description
    Relative change in frequency (coughs per hour) versus Placebo
    Time Frame
    Days 7 and 14 versus Baseline
    Title
    24 hour cough frequency
    Description
    Proportion of responders with >=30%, 50% and 75% reduction in frequency versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Awake cough frequency
    Description
    Relative change in frequency (coughs per hour) versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Sleep cough frequency
    Description
    Relative change in frequency (coughs per hour) versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Cough Severity Visual Analogue Scale
    Description
    1 item scale with minimum score of 0 (no cough) to 10 (worst cough) versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Leicester Cough Questionnaire
    Description
    19 item questionnaire with a grading of 1 (all the time ) to 7 (none of the time) versus Placebo
    Time Frame
    Day 21 versus Baseline
    Title
    Patient-Reported Cough Frequency (change)
    Description
    Change versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Patient-Reported Cough Frequency (proportion)
    Description
    Proportion of responders with improvement in at least one category versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Patient Global Impression of Cough Severity
    Description
    1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Patient Global Impression of Cough Change
    Description
    1 item question with a 7 point grading from "much better to much worse" versus Placebo
    Time Frame
    Days 7, 14, and 21 versus Baseline
    Title
    Clinicians Global Impression of Cough Severity
    Description
    1 item question with a grading from "no cough, to mild, moderate or severe" versus Placebo
    Time Frame
    Day 21 versus Baseline (both treatment periods)
    Title
    Clinicians Global Impression of Cough Change
    Description
    1 item question with a 7 point grading from "very much improved to very much worse" versus Placebo
    Time Frame
    Day 21 versus Baseline (both treatment periods)

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Sherry Minor
    Phone
    203-684-1308
    Email
    Sherry.Minor@trevitherapeutics.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Connie Crum, RN
    Phone
    203-599-0265
    Email
    Connie.Crum@trevitherapeutics.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    David Clark, MD
    Organizational Affiliation
    Trevi Therapeutics
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No

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    Refractory Chronic Cough Improvement Via NAL ER (RIVER)

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