Cough Reduction in IPF With Nalbuphine ER
Study Details
Study Description
Brief Summary
This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study.
After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms.
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Arm 1: Placebo
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Arm 2: 27 mg Dose Arm
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Arm 3: 54 mg Dose Arm
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Arm 4: 108 mg Dose Arm Each arm will be titrated to their fixed dose during the blinded 2-week Titration period followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a multi-center randomized, double-blind, placebo-controlled, parallel, 4-arm study.
After meeting eligibility during the Screening Period, subjects will be randomized (1:1:1:1) to one of four treatment arms.
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Arm 1: Placebo
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Arm 2: 27 mg Dose Arm
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Arm 3: 54 mg Dose Arm
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Arm 4: 108 mg Dose Arm Each arm will be titrated to their fixed dose during the blinded 2-week Titration period according to Table: Dosing Scheme, followed by the 4-week Fixed Dose Period for a total of 6 weeks on drug.
Subjects will be taken off study drug at the end of the Fixed Dose Period and followed off treatment for an additional 2 weeks.
If permanent discontinuation of investigational product occurs at any time, the subject should return for discontinuation and safety follow-up visits. They will then be contacted at week 6 by phone to collect information on serious adverse events (SAEs) and vital status.
An independent Data Safety Monitoring Board (DSMB) will periodically review selected data.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 27 mg nalbuphine ER 27 mg nalbuphine ER - titrated |
Drug: nalbuphine ER
Titrated drug 27 mg
|
| Experimental: 54 mg nalbuphine ER 54 mg nalbuphine ER - titrated |
Drug: nalbuphine ER
Titrated drug 54 mg
|
| Experimental: 108 mg nalbuphine ER 108 mg nalbuphine ER - titrated |
Drug: nalbuphine ER
Titrated drug 108 mg
|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Matching placebo
|
Outcome Measures
Primary Outcome Measures
- Effect of NAL ER on 24-hour cough frequency (coughs per hour) [Week 6]
Relative change from Baseline in 24-hour cough frequency versus placebo
Secondary Outcome Measures
- Effect of NAL ER on the EXAcerbation of Chronic pulmonary disease Tool [Week 6]
Relative change from Baseline in the EXACT© question 2 at Week 6 versus placebo
- Safety and tolerability of NAL ER [Screening through 14 day post last dose]
Adverse event, vitals signs, ECGs, clinical laboratory tests, spirometry, physical examinations, Subjective Opiate Withdrawal Scale (SOWS)
- 24-hour cough frequency (Coughs per hour) [Weeks 2, 4, 6]
Relative change from Baseline in 24-hour cough frequency (coughs per hour) versus placebo • Proportion of responders with ≥30%, ≥50% and ≥75% reduction in the 24-hour cough frequency at Week 2, 4, and 6, for NAL ER compared with placebo. • Proportion of responders with ≥30%, ≥50% and ≥75% reduction in the 24-hour cough frequency versus placebo.
- Awake cough frequency (Coughs per hour) [Weeks 2, 4, 6]
Relative change from Baseline in awake cough frequency (coughs per hour) versus lacebo.
- Sleep cough frequency (Coughs per hour) [Weeks 2, 4, 6]
Relative change from Baseline in sleep cough frequency (coughs per hour) at versus placebo.
- EXACT© (EXAcerbation of Chronic pulmonary disease Tool) (EXAcerbation of Chronic pulmonary disease Tool) [Weeks 1, 2, 3, 4, 5, 6]
Change from Baseline in the EXACT© question 2 compared with placebo. Proportion of EXACT© question 2 responders, with response defined as at least a one category improvement versus placebo. Change from Baseline in the EXACT© sub-domains and individual items versusplacebo.
- CS-NRS (Cough Severity Numerical Rating Scale) [Weeks 1, 2, 3, 4, 5, 6]
Change from Baseline in the CS-NRS versus placebo.
- LCQ© (Leicester Cough Questionnaire) [Week 6]
Change from Baseline in the LCQ© total score versus placebo. Proportion of LCQ© responders, with response defined as 1.3-point increase versus placebo
- L-IPF© (Living with Pulmonary Fibrosis Impacts Questionnaire) [Week 6]
Change from Baseline in the L-IPF© versus placebo.
- L-IPF© (Living with Pulmonary Fibrosis Symptoms Questionnaire) [Week 6]
Change from Baseline in the L-IPF© versus placebo.
- EQ-5D-5L™ [Week 6]
Change from Baseline in the EQ-5D-5L™ versus placebo.
- PGI-S Cough (Patient Global Impression of Severity for Cough) [Weeks 2, 4, 6]
1 item measure rating the severity of cough past 7 days No cough, Mild, Moderate or Severe
- PGI-S IPF; (Patient Global Impression of Severity and Change for IPF) [Weeks 2, 4, 6]
1 item measure rating the symptoms of IPF past 7 days No symptoms, Mild, Moderate or Severe
- CGI-S, (Clinicians Global Impression of Severity) [Baseline and Week 6]
A one-item measure evaluating severity of the condition. Not present Very Mild Mild Moderate Moderately Severe Severe Extremely Severe
- PGI-C Cough; (Patient Global Impression of Change for Cough) [Weeks 2, 4, 6]
1 item measure rating the symptoms of IPF. (past 7 days) Much better Moderately better A little better No change A little worse Moderately worse Much worse
- PGI-C IPF (Patient Global Impression of Change in IPF symptoms) [Weeks 2, 4, 6]
1 item measure rating the symptoms of IPF. (Past 7 days) Much better Moderately better A little better No change A little worse Moderately worse Much worse
- CGI-C [Week 6]
A one-item measure evaluating change from the initiation of treatment on a seven point scale. = Very much improved = Much improved = Minimally improved = No change = Minimally worse = Much worse = Very much worse
Eligibility Criteria
Criteria
Inclusion Criteria:
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Diagnosis of IPF as determined by the Principal Investigator based on ATS/ERS/JRS/ALAT guidelines.
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Cough Severity Score ≥ 4 on CS-NRS (Cough Severity Numerical Rating Scale) during the Screening period and Baseline.
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History of chronic cough for at least 8 weeks before screening.
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SpO2 ≥ 92%, taken after at least 5 minutes in a sitting position, undisturbed and non-stimulated (Saturation of Hemoglobin with Oxygen as Measured by Pulse Oximetry).
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FVC ≥ 40% predicted of normal - Forced Vital Capacity, as determined by spirometry adhering to ATS/ERS guidelines.
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DLCO ≥ 25% predicted of normal - Diffusing capacity of the lung for carbon monoxide corrected for hemoglobin, assessed within the last 12 weeks, or at the time of screening.
Exclusion Criteria:
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Currently on continuous oxygen therapy for longer than 16 hours at any level or delivered by any modality. Intermittent oxygen use of any duration over any given 24-hour period is allowed.
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Inadequate swallow reflex as assessed by the ability to sip 3 fluid oz (or 89 mL) of water without coughing or choking.
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Upper or lower respiratory tract infection in the last 8 weeks prior to the baseline visit.
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Clinical history of aspiration pneumonitis.
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Diagnosis of sleep apnea.
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History of major psychiatric disorder.
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History of substance abuse.
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Significant medical condition or other factors that may interfere with the subject's ability to successfully complete the study.
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Pregnant or lactating female subject.
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Known intolerance (gastrointestinal, central nervous system symptoms), hypersensitivity, drug allergy following the use of an opioid drug.
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Use of opiates is prohibited within 14 days prior to the baseline visit.
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Use of benzodiazepines are prohibited within 14 days prior to the baseline visit and for the duration of the study.
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Monoamine oxidase inhibitors (MAOIs) including methylene blue (methylthioninium chloride) and the antibiotic linezolid are prohibited within 14 days prior to the baseline visit and for the duration of the study.
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Use of oral corticosteroid cough treatment is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
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Exposure to any investigational medication, including placebo, is prohibited within 4 weeks prior to the baseline visit and for the duration of the study.
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Medications prescribed as cough suppressants are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
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Use of medications that affect serotonergic neurotransmission and that when used concomitantly with opioids can increase the risk of serotonin syndrome are prohibited unless on a stable dose 14-days prior to the baseline visit and are expected to remain on that dose for the duration of the study.
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Anti-fibrotic medications are prohibited unless on a stable dose for 8 weeks prior to the baseline visit and are expected to remain on that dose for the duration of the study.
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Strong inhibitors/inducers of the P450 Isozymes are prohibited unless on a stable dose for 14-days prior to baseline visit and are expected to remain on that dose for the duration of the study.
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.- NAL03-202