Brief Summary
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.
Brief Title
Evaluation of S-600918 in Adults With Refractory Chronic Cough
Completion Date
Completion Date Type
Actual
Conditions
Chronic Cough
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
P2X3 receptor antagonist
Refractory chronic cough
S-600918
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT04110054
Org Class
Industry
Org Full Name
Shionogi Inc.
Org Study Id
1812VA323
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-selection Study of S-600918 in Patients With Refractory Chronic Cough
Primary Outcomes
Outcome Description
Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour in 24 hours at each visit with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the log-transformed coughs per hour in 24 hours at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.
Outcome Measure
Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment
Outcome Time Frame
Baseline to Week 4
Secondary Outcomes
Outcome Description
The number of coughs per hour for 24 hours was measured using a cough monitor.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment
Outcome Description
Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while awake at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while awake at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment
Outcome Description
The number of coughs per hour while awake was measured using a cough monitor.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment
Outcome Description
Change in cough was calculated based upon the number of coughs per hour in 24 hours at Week 4 and baseline. Results are presented as percent change from baseline. Reported percent change is based on a mixed model for the log-transformed ratio of the number of coughs per hour while asleep at each visit with treatment, week, and treatment-by-week as fixed effect, participants as random effect, and region and the log-transformed coughs per hour while asleep at baseline as covariates. The number of coughs per hour while awake was measured using a cough monitor.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment
Outcome Description
Cough severity was assessed by the participant by a visual analog scale with numbers from 0 to 100. Results are presented as change from baseline. Reported change is based on a mixed model for the change in weekly cough severity score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the severity score at baseline as covariates. Higher scores indicated higher cough severity.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment
Outcome Description
The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the participant 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. Higher score indicates a better quality of life. Results are presented as change from baseline. Reported change is based on a mixed model for the change in LCQ Total Score after 4 weeks of treatment with treatment, week, and treatment-by-week as fixed effect, participant as random effect, and region (Japan, Europe, or the United States) and the LCQ Score of corresponding domain at baseline as covariates.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score
Outcome Description
The LCQ is a patient-reported quality of life (QOL) measure of chronic cough. The questionnaire consists of 19 items to which the participant 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 - 2. A higher score indicates a better quality of life.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points
Outcome Description
The ICIQ-SF is a questionnaire used to evaluate the frequency, severity, and impact of urinary incontinence on the quality of life. The questionnaire includes 3 items with responses measured on Likert scales, and 1 item that is measured via a qualitative response. The 3 nominal responses are summed to give the ICIQ score (this total ICIQ-SF score can range from 0 to 21), where a higher score indicates more severe symptoms. The 1 item remaining that is measured via qualitative response is not given a score; rather, the participant selects 1 description out of 8 possible descriptions of this item.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)
Outcome Description
The SF-36 is a 36-item questionnaire to assesses a participant's health status using 8 health concepts: limitations in physical activities because of health problems; limitations in social activities because of physical or emotional problems; limitations in usual role activities because of physical health problems; bodily pain; general mental health (psychological distress and well-being); limitations in usual role activities because of emotional problems; vitality (energy and fatigue); and general health perceptions. The mental component reports the average of all the emotionally relevant items and the physical component reports the average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 indicates no disability. Median change can range from -100 to 100. A positive median change indicates an improved outcome.
Outcome Time Frame
Baseline to Week 4
Outcome Measure
Change From Baseline in Short Form (36) Health Survey (SF-36)
Outcome Description
The PGIC is a patient-reported measure of overall health status and consists of 1 item adapted from the Clinical Global Impressions scale. The participant selects 1 description out of 7 possible descriptions of this item. The descriptions are numbered from 1 through 7, where lower numbers indicate better quality of life. Participants were considered responders if they reported "Very much improved", "Much improved", or "Minimally improved" from baseline on the PGIC assessment.
Outcome Time Frame
Week 4
Outcome Measure
Number of Responders as Assessed by Patient Global Impression of Change (PGIC)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Golda Hudes
Investigator Email
ghudes@montefiore.org
Investigator Phone
646-229-9509