Evaluation of S-600918 in Adults With Refractory Chronic Cough

Study Overview
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Brief Summary
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The primary objective of this study is to determine the optimal dose of S-600918 in patients with refractory chronic cough by evaluating the change from baseline in 24-hour cough frequency (coughs per hour) with S-600918 compared with placebo.

Official Title
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A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-selection Study of S-600918 in Patients With Refractory Chronic Cough

Conditions
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Chronic Cough

Intervention / Treatment
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* Drug: S-600918
* Drug: Placebo to S-600918


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Having refractory chronic cough (including unexplained chronic cough) for at least 1 year. If female and of childbearing potential, agreement to use one of the allowed contraceptive methods. Capable of giving signed informed consent. Key Exclusion Criteria: Currently smokes or uses potentially irritating inhalational agents (eg, e-cigarettes, smokeless cigarettes, vaping); stopped smoking or using potentially irritating inhalational agents within the last year; or has a smoking history of 20 pack-years or more. Has chronic obstructive pulmonary disease or uncontrolled asthma. Has a clinically unstable medical condition. History of or ongoing significant psychiatric disorder. History of respiratory tract infection or significant change in lung function or a pulmonary condition in the last 4 weeks. History of malignancy in the last 5 years. History of severe drug allergy. History of alcohol or drug abuse in the last year or currently uses any form of marijuana or illicit drugs. Has a clinically significant finding on a chest x-ray or chest computed tomography (CT) scan in the last year. Has systolic blood pressure > 160 mm Hg or diastolic blood pressure > 90 mm Hg. Received S-600918 previously. Received an investigational drug in the last 3 months. Received an angiotensin converting enzyme (ACE) inhibitor in the last 3 months or requires such treatment. Has a positive serologic test for human immunodeficiency virus (HIV) antigen or antibody, hepatitis B virus surface antigen, or hepatitis C virus ribonucleic acid (RNA). If female, pregnant or trying to become pregnant or breastfeeding.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-600918 50 mg<br>Participants will receive 50 mg S-600918 orally once a day for 28 days. | Drug: S-600918<br>* Tablets for oral administration<br>* Other names: Sivopixant;|
| Experimental: S-600918 150 mg<br>Participants will receive 150 mg S-600918 orally once a day for 28 days. | Drug: S-600918<br>* Tablets for oral administration<br>* Other names: Sivopixant;|
| Experimental: S-600918 300 mg<br>Participants will receive 300 mg S-600918 orally once a day for 28 days. | Drug: S-600918<br>* Tablets for oral administration<br>* Other names: Sivopixant;|
| Placebo Comparator: Placebo<br>Participants will receive placebo to S-600918 orally once a day for 28 days. | Drug: Placebo to S-600918<br>* Tablets for oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cough at Week 4 Calculated as the Ratio of Number of Coughs per Hour in 24 Hours at Week 4 to Baseline | The number of coughs per hour for 24 hours will be measured using a cough monitor. | Baseline and Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour in 24 Hours by ≥ 30% | The number of coughs per hour for 24 hours will be measured using a cough monitor. | Baseline and Week 4 | 
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour in 24 Hours by ≥ 50% | The number of coughs per hour for 24 hours will be measured using a cough monitor. | Baseline and Week 4 | 
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour in 24 Hours by ≥ 70% | The number of coughs per hour for 24 hours will be measured using a cough monitor. | Baseline and Week 4 | 
| Change in Cough at Week 4 Calculated as the Ratio of the Number of Coughs per Hour While Awake at Week 4 to Baseline | The number of coughs per hour while awake will be measured using a cough monitor. | Baseline and Week 4 | 
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour While Awake by ≥ 30% | The number of coughs per hour while awake will be measured using a cough monitor. | Baseline and Week 4 | 
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour While Awake by ≥ 50% | The number of coughs per hour while awake will be measured using a cough monitor. | Baseline and Week 4 | 
| Percentage of Participants with a Reduction from Baseline in the Number of Coughs per Hour While Awake by ≥ 70% | The number of coughs per hour while awake will be measured using a cough monitor. | Baseline and Week 4 | 
| Change in Cough at Week 4 Calculated as the Ratio of the Number of Coughs per Hour While Asleep at Week 4 to Baseline | The number of coughs per hour while asleep will be measured using a cough monitor. | Baseline and Week 4 | 
| Change from Baseline in Weekly Cough Severity | Cough severity will be assessed by the participant on a 100 mm visual analog scale where higher scores indicate worse severity. | Baseline and Week 4 | 
| Change from Baseline through Day 7 in Daily Cough Severity | Cough severity will be assessed by the participant on a 100 mm visual analog scale where higher scores indicate worse severity. | Baseline and Day 7 | 
| Change from Baseline in Leicester Cough Questionnaire (LCQ) | The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the patient responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 21; a higher score indicates a better quality of life. | Baseline and Week 4 | 
| Percentage of Participants with an Increase in LCQ of ≥ 1.3 points | The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the patient responds on a 7-point Likert response scale (from 1 to 7). Each item assesses symptoms during cough and the effect of cough on 3 main domains: physical, psychological and social. Domain scores range from 1-7, and the total score ranges from 3 - 21; a higher score indicates a better quality of life. | Baseline and Week 4 | 
| Change from Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | The ICIQ-SF is a patient-reported measure of the severity of urinary incontinence and quality of life (QOL) for those with urinary incontinence. The questionnaire consists of 4 items that evaluate the frequency, severity, and impact of urinary incontinence on QOL. A total score ranging from 0-21 is possible for 3 of the 4 items combined, where a higher score indicates more severe symptoms. The 1 item remaining is not given a score; rather, the patient selects one description out of 8 possible descriptions of this item. | Baseline and Week 4 | 
| Change from Baseline in Short Form (36) Health Survey (SF-36) | The SF-36 is a patient-reported measure of overall health status. The questionnaire consists of 8 scaled scores (health concepts) and evaluates vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Scores for each scale range from 0 to 100; the lower the score, the greater the disability. | Baseline and Week 4 | 
| Patient Global Impression of Change (PGIC) | The PGIC is a patient-reported measure of overall health status and consists of one item adapted from the Clinical Global Impressions scale. The patient selects one description out of 7 possible descriptions of this item. The descriptions are numbered from 1 through 7, where the most favorable description is numbered as 1 and the least favorable description is numbered as 7. | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P2X3 receptor antagonist, Refractory chronic cough, S-600918