A Dose Escalation Study of BLU-5937 in Unexplained or Refractory Chronic Cough

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind, placebo-controlled, crossover, dose escalation study of BLU-5937 in subjects with unexplained or refractory chronic cough

Detailed Description
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This study will have two 16-day treatment periods (four escalating doses or matching placebo at four days interval) separated by a 10 to 14-day washout period. There will be a 14-day follow-up period.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Crossover, Dose Escalation Study of BLU-5937 in Subjects With Unexplained or Refractory Chronic Cough (RELIEF)

Conditions
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Chronic Refractory Cough

Intervention / Treatment
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* Drug: BLU-5937
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unexplained or refractory chronic cough for at least one year Chest radiograph or CT thorax within the last 60 months not demonstrating any abnormality considered to be significantly contributing to the chronic cough Cough count of ≥ 10 per hour (Awake Cough Count) at Screening Score of ≥ 40mm on the Cough Severity VAS at Screening Women of child-bearing potential must have a negative serum pregnancy test at Screening Women of child-bearing potential must use a highly effective contraception method from Screening through the Follow-Up Visit Male subjects and their partners of child-bearing potential must use 2 methods of acceptable birth control Exclusion Criteria: Current smoker or individuals who have given up smoking within the past 6 months, or those with >20 pack-year smoking history Diagnosis of COPD, bronchiectasis, idiopathic pulmonary fibrosis Treatment with an ACE-inhibitor as the potential cause of a subject's cough, or requiring treatment with an ACE-inhibitor during the study, or within 12 weeks prior to the Screening Visit FEV1/FVC < 60% History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening History of a diagnosis of drug or alcohol dependency or abuse within the last 3 years Clinically significant abnormal electrocardiogram (ECG) or laboratory tests at Screening Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results

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: Two-arm, Two-Period, crossover assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BLU-5937 oral tablet BID<br>Randomized crossover design of 4 different doses (25, 50, 100, 200 mg BID) of BLU-5937 tablets to be administered orally BID | Drug: BLU-5937<br>* Four escalating doses of BLU-5937 administered BID over the course of the study<br>|
| Placebo Comparator: Placebo oral tablet BID<br>Randomized crossover design of matching placebo tablets to be administered orally BID | Drug: Placebo<br>* Matching placebo for BLU-5937<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Awake Objective Cough Frequency on Log-transformed Scale | Change in awake cough frequency (average hourly cough frequency while the subject is awake ) evaluated using the VitaloJAK cough monitor with 24-hour sound recordings collected | Period 1: baseline (Day 0) and 24 hours after Day 4, 8, 12, 16 doses ; Period 2: baseline (Day 30) and 24 hours after Day 34, 38, 42, 46 doses | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unexplained or refractory chronic cough, P2X3 antagonists