Cough Reduction in Patients With Refractory Chronic Cough Following Administration of NAL ER Versus Placebo
Study Details
Study Description
Brief Summary
A 2-period study for the treatment of cough in patients with Refractory Chronic Cough.
If eligible for the study, patients will be randomly assigned to either:
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study drug in Treatment Period 1, followed by Placebo (no drug) in Treatment Period 2 OR
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Placebo in Treatment Period 1, followed by study drug in Treatment Period 2. Neither the site staff nor the patient will know which treatment they are receiving in either period.
Each period will last 21 days and are separated by 21 days. The study drug doses will be increased gradually during the study periods.
Following a screening visit to determine if a patient is eligible for the study, visits in each treatment period will be at Day -1 (Baseline), and at Days 6, 13, and 20.
Patients will be taken off study drug at the end of the Treatment Period 2 and followed for an additional 2 weeks.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
A double-blind, randomized, placebo-controlled, 2-period crossover study for the treatment of cough 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 (1:1) to one of the following sequences:
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NAL- ER in Treatment Period 1, followed by Placebo (PBO) in Treatment Period 2 OR
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PBO-NAL in Treatment Period 1, followed by NAL ER in Treatment Period 2.
The 21-day treatment periods are separated by a 21-day washout period. NAL ER will be titrated.
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 diary.
Subjects will be taken off study drug at the end of the Treatment Period 2 and followed off treatment for an additional 2 weeks.
If permanent discontinuation of investigational product occurs at any time, the subject should return for a discontinuation visit, and then be asked to attend all visits and undergo all examinations as originally planned. For subjects who do not attend all visits, a safety follow up visit will be performed, and information on serious adverse events over the 6 weeks and vital status at week 6 will be determined.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NAL ER NAL ER, tablets, 27 mg QD to BID, 54 mg BID, 108 mg BID, 2 periods of 21 days each |
Drug: Nalbuphine Hydrochloride
Oral tablets
Other Names:
|
| Placebo Comparator: Placebo Placebo, tablets, 0 mg QD to BID, 0 mg BID, 0 mg BID, 2 periods of 21 days each |
Drug: Placebo
Oral tablets
|
Outcome Measures
Primary Outcome Measures
- 24 hr cough frequency [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 [Baseline through follow-up]
Adverse events, clinical labs, vital signs, physical exams, electrocardiograms
- Subjective Opiate Withdrawal Scale [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 [Days 7 and 14 versus Baseline]
Relative change in frequency (coughs per hour) versus Placebo
- 24 hour cough frequency [Days 7, 14, and 21 versus Baseline]
Proportion of responders with >=30%, 50% and 75% reduction in frequency versus Placebo
- Awake cough frequency [Days 7, 14, and 21 versus Baseline]
Relative change in frequency (coughs per hour) versus Placebo
- Sleep cough frequency [Days 7, 14, and 21 versus Baseline]
Relative change in frequency (coughs per hour) versus Placebo
- Cough Severity Visual Analogue Scale [Days 7, 14, and 21 versus Baseline]
1 item scale with minimum score of 0 (no cough) to 10 (worst cough)
- Leicester Cough Questionnaire [Day 21 versus Baseline]
19 item questionnaire with a grading of 1 (all the time ) to 7 (none of the time)
- Patient-Reported Cough Frequency (change) [Days 7, 14, and 21 versus Baseline]
Change versus Placebo
- Patient-Reported Cough Frequency (proportion) [Days 7, 14, and 21 versus Baseline]
Proportion of responders with improvement in at least one category versus Placebo
- Patient Global Impression of Severity and Change for Cough [Days 7, 14, and 21 versus Baseline]
Change versus Placebo
- Clinicians Global Impression of Severity and Change [Day 21 versus Baseline]
Change versus Placebo
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Diagnosis of refractory chronic cough (RCC) for at least one year
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Chest radiograph or CT of thorax within 24 months or during screening not demonstrating any significant abnormalities contributing to RCC
Exclusion Criteria:
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Diagnosis of sleep apnea
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Respiratory tract infection within 6 weeks of Baseline
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History of bronchiectasis, COPD, or IPF
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History of uncontrolled asthma
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Current smokers/vapers, quit smoking with <=12 months, using nicotine supplements, or history of >=20 pack years
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History of major psychiatric disorder
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History of substance abuse
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Pregnant or lactating females
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Known intolerance to opioids
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Previous participation in a nalbuphine ER clinical study
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Use of opiates, benzodiazepines, or MAOIs within 14 days of Baseline
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Use of pregabalin, gabapentin, thalidomide for treatment of cough within 14 days of Baseline
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Use of ACE inhibitors within 12 weeks of Baseline
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Use of unstable doses of cough suppressants within 14 days of Baseline
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Use of unstable doses of medications that affect serotonergic neurotransmission that may cause serotonin syndrome with opioids within14 days of Baseline
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Use of unstable doses of P450 isozyme inhibitors/inducers within 14 days of Baseline
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Trevi Therapeutics
Investigators
- Study Director: David Clark, MD, Trevi Therapeutics
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NAL04-201