A Study of Efficacy and Safety of AX-8 in Chronic Cough

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, crossover, multicenter study of AX-8 in participants with unexplained or refractory chronic cough designed to evaluate the effectiveness of AX-8 in reducing cough frequency.

Official Title
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A Phase 2 Study to Assess the Efficacy and Safety of AX-8 in Patients With Chronic Cough

Conditions
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Chronic Cough

Intervention / Treatment
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* Drug: AX-8
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chest radiograph or computed tomography (CT) of the thorax approximately 12 months before screening not demonstrating any abnormality considered to be significantly contributing to the chronic cough Have a diagnosis of refractory chronic cough (RCC) or unexplained chronic cough (UCC) for at least one year Women of childbearing potential and their male partners must use 2 acceptable methods of contraception Male subjects and their female partners of childbearing potential must use 2 acceptable methods of contraception Have provided written informed consent Exclusion Criteria: Positive diagnostic nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Current smoker (including e-cigarettes), individuals who have given up smoking within the past 12 months, or individuals with a smoking history of 20 pack-years 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 Baseline Visit History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks History of cystic fibrosis Positive test for any drug of abuse History of malignancy within 5 years prior to the Baseline Visit History of infection or known active infection with human immunodeficiency (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) History of hypersensitivity or intolerance to AX-8 or other TRPM8 agonists or any of the excipients

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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AX-8 to Placebo<br>AX-8 BID, taken for 2 weeks, followed by a 1-week washout period and then Placebo BID, taken for 2 weeks. | Drug: AX-8<br>* orally disintegrating tablets, BID<br>Drug: Placebo<br>* orally disintegrating tablets, BID<br>|
| Experimental: Placebo to AX-8<br>Placebo BID, taken for 2 weeks, followed by a 1-week washout period and then AX-8 BID, taken for 2 weeks. | Drug: AX-8<br>* orally disintegrating tablets, BID<br>Drug: Placebo<br>* orally disintegrating tablets, BID<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in objective cough frequency in the 8 hours after the first dose of the day (i.e., Dose 1) on the 1st day of treatment of each study period | Assessment of number of coughs per hour to be evaluated using a digital recording device | Baseline (i.e., Days -1 and 22) and the 1st day of treatment (i.e., Days 1 and 23) of each study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in awake cough frequency | 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 | Baseline (i.e., Days -1 and 22), the 1st day of treatment (i.e., Days 1 and 23) and the 14th day of treatment (i.e., Days 14 and 36) of each study period | 
| Change from Baseline in Cough Severity Visual Analog Scale (VAS) score | Cough Severity is determined through the use of a 100 mm visual analogue scale (VAS) (ranging between 0 for no cough and 100 for worst cough). | Baseline (i.e., Days -1 and 22), the 1st day of treatment (i.e., Days 1 and 23) and the 14th day of treatment (i.e., Days 14 and 36) of each study period | 
| Incidence (percent of participants) of treatment-emergent adverse events (TEAEs) | TEAEs are defined as those AEs (i.e., a new event or an exacerbation of a pre-existing condition) occurring on or after the first study dosing (i.e., Dose 1 on Day 1). | From first dose of study drug (i.e., Dose 1 on Day 1) to follow-up visit (i.e., Day 50, included) | 
| Incidence (percent of participants) of serious adverse events (SAEs) | An SAE is an adverse events occurring during any study phase and that fulfils one or more of the following: results in death, is life-threatening, requires patient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a significant or important medical event, or is a congenital anomaly/birth defect in the offspring of a subject who received study drug. | From screening visit (i.e., Days -21 to -2) to follow-up visit (i.e., Day 50, included) |