Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

Study Overview
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Brief Summary
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Study of the efficacy, safety, and tolerability of serlopitant for the treatment of refractory chronic cough

Official Title
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A Randomized, Double-blind, Placebo-controlled Study of the Efficacy, Safety, and Tolerability of Serlopitant for the Treatment of Refractory Chronic Cough

Conditions
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Refractory Chronic Cough

Intervention / Treatment
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* Drug: 5 mg Serlopitant Tablets
* Drug: Matching Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female and males between 18 and 80 years of age Have a diagnosis of treatment refractory chronic cough or unexplained cough for at least one year Chest radiograph or computed tomography (CT) Thorax within the last 5 years not demonstrating any abnormality considered to be significantly contributing to the chronic cough At Screening have a score of ≥ 40mm on the Cough Severity VAS At Baseline (Day 0) have a score of ≥ 40mm on the Cough Severity VAS All female subjects who are of childbearing potential must practice highly effective contraception (i.e., pregnancy prevention method with a failure rate of < 1% per year) from the time of the initial screening visit until 4 weeks after last dose of study drug. Please refer to the protocol for acceptable methods of contraception Exclusion Criteria: Prior treatment with serlopitant or other NK1-R antagonist Presence of any medical condition or disability that could interfere with study History of hypersensitivity to serlopitant or any of its components Currently pregnant or male partner of pregnant female Females of childbearing potential who are unable or unwilling to use adequate contraception or who are breast feeding Current smoker or individuals who have given up smoking within the past 12 months FEV1/FVC < 60% Body mass index (BMI) <18 kg/m2 or ≥ 40 kg/m2 at Screening History of upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day 0) History of cystic fibrosis History of opioid use within 1 week of the Baseline Visit (Day 0) Requiring concomitant therapy with prohibited medications Treatment with biologic therapies within 8 weeks or 5 half-lives prior to the Baseline Visit (Day 0), whichever is longer Treatment with strong CYP3A4 inhibitors within 4 weeks prior to the Baseline Visit (Day 0) Treatment with any investigational therapy within 4 weeks (investigational biologic therapies within 8 weeks) prior to the Baseline Visit (Day 0) Serum creatinine, total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2x the upper limit of normal (ULN) during screening Positive test for any drug of abuse History of malignancy within 5 years prior to the Baseline Visit (Day 0), with the exception of completely treated and non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin Any known psychiatric diagnosis meeting DSM-5 criteria which may confound the assessment of serlopitant safety or efficacy, or interfere with the subject's ability to comply with protocol-mandated activities, within 3 years prior to randomization. Examples of such DSM-5 diagnoses include but are not limited to major depressive disorder, bipolar disorder, schizophrenia, psychotic disorder, intellectual disability, severe alcohol use disorder. Known active hepatitis infection Known history of human immunodeficiency virus (HIV) infection

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 mg Serlopitant Tablets<br>Serlopitant Tablets | Drug: 5 mg Serlopitant Tablets<br>* Serlopitant Tablets<br>* Other names: VPD-737;|
| Placebo Comparator: Matching Placebo Tablets<br>Placebo Tablets | Drug: Matching Placebo Tablets<br>* Placebo Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24-hour Objective Cough Frequency (Log Normalized Percent Change Relative to Placebo) | Change in 24-hour objective cough frequency is total number of cough events during the monitoring period (24-hour interval)/24 (Total duration (in hours) for the monitoring period) which is captured through sound recordings by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd). | from Baseline to Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Awake Objective Cough Frequency | Awake cough frequency = (total number of cough events during the monitoring period (24-hour interval) the subject is awake)/(Total duration (in hours) for the monitoring period the subject is awake) which is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd). | from Baseline to Day 84 | 
| Percentage of Participants With ≥ 30% Reduction in 24-hour Objective Cough Frequency | The percentage of participants with ≥ 30% of reduction from baseline in 24-hour cough frequency is the number of participants with ≤-30% change in 24-hour cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd). | from Baseline to Day 84 | 
| Percentage of Participants With ≥30% Reduction in Awake Objective Cough Frequency | The percentage of participants with ≥ 30% of reduction from baseline in the awake cough frequency is the number of participants with ≤30% change in awake cough frequency divided by the total number of participants with available data. This data is captured by a custom-built digital recording device (VitaloJAK, Vitalograph, Ltd). | from Baseline to Day 84 | 
| Change From Baseline in Cough Severity Visual Analog Scale (VAS) | Visual Analog Scale (VAS) 101-point scale ranging from 0 (no cough) to 100 (worst cough). A higher score corresponds to higher cough severity. | from Baseline to Day 84 |