A Study of Nalbuphine (Extended Release) ER in Idiopathic Pulmonary Fibrosis (IPF) for Treatment of Cough

Study Overview
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Brief Summary
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To investigate the efficacy and safety of Nalbuphine ER (NAL ER) tablets in subjects diagnosed with Idiopathic Pulmonary Fibrosis (IPF) and evaluate it's treatment of cough in these patients. This is a two-treatment, 2-period crossover study. Subjects will be randomized in Treatment Period 1 to either NAL ER or matching placebo and evaluated for approximately 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
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This is a double-blind, randomized, placebo-controlled, 2-treatment, 2-period crossover efficacy and safety study in IPF subjects with NAL ER tablets for the treatment of cough. The study consists of 2 treatment periods of 3 weeks, each followed by a washout period of 2 weeks. Treatment Period 1: During Treatment Period 1, eligible subjects will be randomized (1:1) to one of the following treatment arms: Arm 1: Active NAL ER followed by crossover Placebo in Treatment Period 2 Arm 2: Placebo followed by crossover NAL ER in Treatment Period 2 Following 3 weeks of dosing in Treatment Period 1, subjects will complete a 2-week washout period before entering Treatment Period 2. Subjects assigned to Arm 1 will receive placebo and subjects assigned to Arm 2 will receive NAL ER during Treatment Period 2. A final 2-week washout period will occur at the completion of Treatment Period 2. NAL ER Dosing Subjects on NAL ER will have the dose titrated from 27 mg once daily (QD) to 54 mg twice a day (BID) over a 5-day period and then maintained at 54 mg twice a day (BID) for approximately 4 days. Doses will be subsequently escalated and maintained at 108 mg twice a day (BID) over 1 week and then to 162 mg twice a day (BID) over 6 days.

Official Title
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Phase 2, Double-blind, Randomized, Placebo-controlled, Two-Treatment, Two-Period Crossover Efficacy and Safety Study in Idiopathic Pulmonary Fibrosis (IPF) With Nalbuphine ER Tablets for the Treatment of Cough

Conditions
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Nalbuphine, Idiopathic Pulmonary Fibrosis, Cough

Intervention / Treatment
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* Drug: NAL ER
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals diagnosed with Idiopathic Pulmonary Fibrosis Chronic cough > 8 weeks. Daytime cough severity score ≥ 4 on Cough Severity Numerical Rating Scale at screening Exclusion Criteria: The following conditions are excluded: Interstitial lung disease (ILD) known to be caused by domestic and occupational environmental exposures. Interstitial lung disease (ILD) known to be caused by connective tissue disease. Interstitial lung disease (ILD) known to be caused by drug related toxicity. 2. Currently on continuous oxygen therapy. 3. History of substance abuse that, as determined by the Investigator, may interfere with the conduct of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized, double-blinded, placebo-controlled, 2-Treatment, 2-Period Crossover Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NAL ER then placebo<br>Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period, followed by a 2 week washout. They will then receive Placebo tablet (matching NAL ER BID) for 3 weeks. | Drug: NAL ER<br>* Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period.<br>* Other names: Nalbuphine;Drug: Placebo<br>* Participants will receive Placebo tablet (matching NAL ER BID) over a 3 week period.<br>* Other names: Nalbuphine;|
| Experimental: Placebo then NAL ER<br>Participants will receive Placebo tablet (matching NAL ER BID) for 3 weeks, followed by a 2 week washout. They will then receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period . | Drug: NAL ER<br>* Participants will receive NAL ER 27 mg QD, 27 mg BID, 54 mg BID, 108 mg BID, 162 mg BID over a 3 week period.<br>* Other names: Nalbuphine;Drug: Placebo<br>* Participants will receive Placebo tablet (matching NAL ER BID) over a 3 week period.<br>* Other names: Nalbuphine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of percentage of responders by Treatment | To evaluate the effect of Nalbuphine ER tablets on the mean daytime cough frequency (coughs per hour) at day 22 (dose 162 mg twice daily [BID]) as compared to placebo. Daytime is defined as the period between the time the subject reported being awake and the time the subject went to bed. Assessment is done using objective digital cough monitoring. | Up to 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline daytime cough frequency effect of escalating doses of Nalbuphine ER | To evaluate the effect of escalating doses of Nalbuphine ER on the mean relative change from baseline in daytime cough frequency (coughs per hour) at day 9 (dose: 54 mg BID), day 16 (dose: 108 mg BID) and day 22 (dose: 162 mg BID). | Up to 3 weeks | 
| Comparison of percentage of responders on the Evaluating Respiratory Symptoms (E-RS™) diary cough scale | The E-RS will be used to look at the percentage of responders with response defined as at least one category improvement from baseline. | Up to 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nalbuphine, Cough, Idiopathic Pulmonary Fibrosis, Pharmacokinetics