A Dose Escalation Study of Bradanicline in Refractory Chronic Cough

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, crossover, dose escalation study of bradanicline in subjects with chronic cough

Detailed Description
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This study will have two 21-day treatment periods separated by a 14-day washout period. There will be a 14-day follow-up period.

Official Title
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A Dose Escalation Study to Assess the Efficacy and Safety of Bradanicline in Subjects With Refractory Chronic Cough

Conditions
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Chronic Cough

Intervention / Treatment
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* Drug: Bradanicline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chest radiograph or computed tomography (CT) scan of the thorax within the last 1 year not demonstrating any abnormality considered to be significantly contributing to the refractory chronic cough Diagnosis of refractory chronic cough or unexplained cough for at least one year Women of child-bearing potential who use 2 forms of acceptable birth control method Male subjects and their partners of child-bearing potential who use 2 methods of acceptable birth control Has provided written informed consent Exclusion Criteria: Current smoker (cigarettes or e-cigarettes) or has given up smoking within the past 12 months Currently taking an ACE-inhibitor or requiring treatment with an ACE-inhibitor during the study or within 12 weeks prior to the Baseline Visit Has an upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit Has a history of cystic fibrosis Has a history of malignancy within 5 years prior to the Baseline Visit Has active hepatitis infection Has a history of human immunodeficiency virus (HIV) infection Has a positive test for any drug of abuse Has a history of hypersensitivity to bradanicline or any of its components

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bradanicline QD<br>Randomized crossover design of 3 different doses of bradanicline (film-coated tablets) to be administered orally QD | Drug: Bradanicline<br>* Three different doses over the course of the study<br>Drug: Placebo<br>* Matching placebo for Bradanicline<br>|
| Placebo Comparator: Placebo<br>Randomized crossover design of matching placebo tablets to be administered orally QD | Drug: Bradanicline<br>* Three different doses over the course of the study<br>Drug: Placebo<br>* Matching placebo for Bradanicline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Awake coughs per hour at Days 7, 14, 21, 43, 50, 57 | Assessment of awake coughs per hour (average hourly cough frequency while the participant is awake based on sound recordings), to be evaluated using a digital recording device | Change from Baseline at Days 7, 14, 21, 43, 50, 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour coughs per hour at Days 7, 14, 21, 43, 50, 57 | Assessment of 24-hour coughs per hour (average hourly cough frequency based on 24-hour sound recordings), to be evaluated using a digital recording device | Change from Baseline at Days 7, 14, 21, 43, 50, 57 | 
| Percentage of participants who have at least one adverse event (AE) during the treatment periods, washout, and follow-up | Assessment of participants who have at least one AE during treatment period 1 (21 days), during washout (14 days), during treatment period 2 (21 days), and follow-up (14 days) | up to 57 days |