Chronic Cough
Conditions
Keywords
P2X3 receptor antagonist, Refractory chronic cough, S-600918
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.
Interventions
DRUGS-600918
Tablets for oral administration
DRUGPlacebo to S-600918
Tablets for oral administration
Sponsors
Shionogi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment | Baseline to Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment | Baseline to Week 4 | 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. |
| Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | Baseline to Week 4 | The number of coughs per hour while awake was measured using a cough monitor. |
| Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment | Baseline to Week 4 | 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. |
| Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment | Baseline to Week 4 | 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. |
| Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | Baseline to Week 4 | The number of coughs per hour for 24 hours was measured using a cough monitor. |
| Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points | Baseline to Week 4 | 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. |
| Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline to Week 4 | 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. |
| Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline to Week 4 | 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. |
| Number of Responders as Assessed by Patient Global Impression of Change (PGIC) | Week 4 | 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. |
| Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score | Baseline to Week 4 | 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. |
Countries
Czechia, Japan, Poland, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| S-600918 50 mg Participants received 50 mg S-600918 tablets orally once daily for 28 days | 100 |
| S-600918 150 mg Participants received 150 mg S-600918 tablets orally once daily for 28 days | 102 |
| S-600918 300 mg Participants received 300 mg S-600918 tablets orally once daily for 28 days | 96 |
| Placebo Participants received placebo tablets orally once daily for 28 days | 102 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 4 | 3 |
| Overall Study | COVID-19 reason other than AE | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | S-600918 300 mg | Placebo | Total | S-600918 50 mg | S-600918 150 mg |
|---|---|---|---|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 12.4 | 56.1 years STANDARD_DEVIATION 11.5 | 57.0 years STANDARD_DEVIATION 11.9 | 58.7 years STANDARD_DEVIATION 11.2 | 57.2 years STANDARD_DEVIATION 12.5 |
| Average Coughs per Hour in 24 Hours | 36.21 number of coughs STANDARD_DEVIATION 37.91 | 33.85 number of coughs STANDARD_DEVIATION 34.6 | 35.36 number of coughs STANDARD_DEVIATION 43 | 30.40 number of coughs STANDARD_DEVIATION 22.92 | 40.95 number of coughs STANDARD_DEVIATION 64.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 2 Participants | 14 Participants | 5 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 92 Participants | 100 Participants | 385 Participants | 95 Participants | 98 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 25 Participants | 22 Participants | 97 Participants | 25 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 9 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 69 Participants | 72 Participants | 288 Participants | 71 Participants | 76 Participants |
| Sex: Female, Male Female | 65 Participants | 77 Participants | 295 Participants | 78 Participants | 75 Participants |
| Sex: Female, Male Male | 31 Participants | 25 Participants | 105 Participants | 22 Participants | 27 Participants |
| Weekly Severity of Cough | 72.6 score on a scale STANDARD_DEVIATION 15.3 | 71.6 score on a scale STANDARD_DEVIATION 14.5 | 73.1 score on a scale STANDARD_DEVIATION 14.4 | 74.8 score on a scale STANDARD_DEVIATION 14 | 73.6 score on a scale STANDARD_DEVIATION 13.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 0 / 103 | 0 / 100 | 0 / 102 |
| other Total, other adverse events | 5 / 101 | 15 / 103 | 34 / 100 | 10 / 102 |
| serious Total, serious adverse events | 0 / 101 | 0 / 103 | 0 / 100 | 0 / 102 |
Outcome results
Primary
Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| S-600918 50 mg | Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment | -55.16 percentage change |
| S-600918 150 mg | Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment | -61.08 percentage change |
| S-600918 300 mg | Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment | -65.32 percentage change |
| Placebo | Percent Change in Number of Coughs Per Hour in 24 Hours Following 4 Weeks of Study Treatment | -60.38 percentage change |
Comparison: The null hypotheses of equality between the treatment and placebo effects were tested using a mixed model, containing treatment group, week, and interaction between treatment groups and week as fixed effects; participant as random effect; and region and the common logarithm of the frequency of coughs per hour at baseline as covariates. Covariance structure was given as unstructured.p-value: 0.9334ANCOVA
Secondary
Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF)
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe for this specific outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female With Symptoms | 9.9 score on a scale | Standard Deviation 5 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female With Symptoms | -2.2 score on a scale | Standard Deviation 3.9 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female Without Symptoms | 0.9 score on a scale | Standard Deviation 2.2 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male With Symptoms | 9.5 score on a scale | Standard Deviation 5.3 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male With Symptoms | -2.0 score on a scale | Standard Deviation 8.3 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 50 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male Without Symptoms | 0.8 score on a scale | Standard Deviation 2.4 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male With Symptoms | -0.7 score on a scale | Standard Deviation 2.7 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male With Symptoms | 5.0 score on a scale | Standard Deviation 2.3 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female With Symptoms | -1.2 score on a scale | Standard Deviation 3.4 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male Without Symptoms | 1.3 score on a scale | Standard Deviation 3.2 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female Without Symptoms | 0.1 score on a scale | Standard Deviation 0.4 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 150 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female With Symptoms | 8.8 score on a scale | Standard Deviation 5.2 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female Without Symptoms | 0.5 score on a scale | Standard Deviation 1.3 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male With Symptoms | 6.7 score on a scale | Standard Deviation 4 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male With Symptoms | -1.0 score on a scale | Standard Deviation 2.3 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male Without Symptoms | 0.5 score on a scale | Standard Deviation 1.4 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female With Symptoms | 9.2 score on a scale | Standard Deviation 4.6 |
| S-600918 300 mg | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female With Symptoms | -1.6 score on a scale | Standard Deviation 3.8 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female Without Symptoms | 0.3 score on a scale | Standard Deviation 1.1 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Female With Symptoms | -1.2 score on a scale | Standard Deviation 3.3 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Female With Symptoms | 8.6 score on a scale | Standard Deviation 4.2 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male With Symptoms | 5.0 score on a scale | Standard Deviation 2.2 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Baseline, Male Without Symptoms | 0.0 score on a scale | Standard Deviation 0 |
| Placebo | Change From Baseline in International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) | Change at Week 4 - Male With Symptoms | -0.9 score on a scale | Standard Deviation 2.2 |
Secondary
Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| S-600918 50 mg | Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score | 2.80 score on a scale |
| S-600918 150 mg | Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score | 3.10 score on a scale |
| S-600918 300 mg | Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score | 3.86 score on a scale |
| Placebo | Change From Baseline in Leicester Cough Questionnaire (LCQ) Total Score | 3.17 score on a scale |
Secondary
Change From Baseline in Short Form (36) Health Survey (SF-36)
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| S-600918 50 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Physical Component Score | 38.4 score on a scale | Standard Deviation 6.3 |
| S-600918 50 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Physical Component Score | -0.3 score on a scale | Standard Deviation 5 |
| S-600918 50 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Mental Component Score | 46.1 score on a scale | Standard Deviation 10.3 |
| S-600918 50 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Mental Component Score | 2.2 score on a scale | Standard Deviation 5.9 |
| S-600918 150 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Physical Component Score | -0.9 score on a scale | Standard Deviation 4.5 |
| S-600918 150 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Mental Component Score | 47.1 score on a scale | Standard Deviation 9 |
| S-600918 150 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Mental Component Score | 1.9 score on a scale | Standard Deviation 6 |
| S-600918 150 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Physical Component Score | 38.6 score on a scale | Standard Deviation 5.7 |
| S-600918 300 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Mental Component Score | 47.5 score on a scale | Standard Deviation 8.7 |
| S-600918 300 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Physical Component Score | -0.9 score on a scale | Standard Deviation 4.6 |
| S-600918 300 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Mental Component Score | 2.6 score on a scale | Standard Deviation 6 |
| S-600918 300 mg | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Physical Component Score | 38.1 score on a scale | Standard Deviation 5.6 |
| Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Mental Component Score | 3.3 score on a scale | Standard Deviation 6 |
| Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) | Change at Week 4 - Physical Component Score | -1.3 score on a scale | Standard Deviation 5 |
| Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Physical Component Score | 37.8 score on a scale | Standard Deviation 5.5 |
| Placebo | Change From Baseline in Short Form (36) Health Survey (SF-36) | Baseline - Mental Component Score | 47.2 score on a scale | Standard Deviation 9.2 |
Secondary
Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| S-600918 50 mg | Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment | -19.99 score on a scale |
| S-600918 150 mg | Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment | -22.95 score on a scale |
| S-600918 300 mg | Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment | -28.29 score on a scale |
| Placebo | Change From Baseline in Weekly Cough Severity Following 4 Weeks of Study Treatment | -21.74 score on a scale |
Secondary
Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment
The number of coughs per hour for 24 hours was measured using a cough monitor.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| S-600918 50 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 30% Reduction | 55 Participants |
| S-600918 50 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 70% Reduction | 24 Participants |
| S-600918 50 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 50% Reduction | 38 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 30% Reduction | 66 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 70% Reduction | 26 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 50% Reduction | 46 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 50% Reduction | 50 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 30% Reduction | 66 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 70% Reduction | 31 Participants |
| Placebo | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 30% Reduction | 61 Participants |
| Placebo | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 70% Reduction | 27 Participants |
| Placebo | Number of Participants With 30%, 50%, and 70% Reduction in Number of Coughs Per Hour Over 24 Hours After 4 Weeks of Study Treatment | ≥ 50% Reduction | 49 Participants |
Secondary
Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment
The number of coughs per hour while awake was measured using a cough monitor.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| S-600918 50 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 30% Reduction | 55 Participants |
| S-600918 50 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 70% Reduction | 22 Participants |
| S-600918 50 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 50% Reduction | 41 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 30% Reduction | 67 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 70% Reduction | 26 Participants |
| S-600918 150 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 50% Reduction | 48 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 50% Reduction | 51 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 30% Reduction | 67 Participants |
| S-600918 300 mg | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 70% Reduction | 29 Participants |
| Placebo | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 30% Reduction | 61 Participants |
| Placebo | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 70% Reduction | 25 Participants |
| Placebo | Number of Participants With 30%, 50% and 70% Reduction in Number of Coughs Per Hour While Awake After 4 Weeks of Study Treatment | ≥ 50% Reduction | 46 Participants |
Secondary
Number of Responders as Assessed by Patient Global Impression of Change (PGIC)
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.
Time frame: Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-600918 50 mg | Number of Responders as Assessed by Patient Global Impression of Change (PGIC) | 57 Participants |
| S-600918 150 mg | Number of Responders as Assessed by Patient Global Impression of Change (PGIC) | 72 Participants |
| S-600918 300 mg | Number of Responders as Assessed by Patient Global Impression of Change (PGIC) | 79 Participants |
| Placebo | Number of Responders as Assessed by Patient Global Impression of Change (PGIC) | 65 Participants |
Secondary
Number of Responders Defined as 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 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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure and 'Number analyzed' = participants evaluable at the specified timeframe.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| S-600918 50 mg | Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points | 53 Participants |
| S-600918 150 mg | Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points | 56 Participants |
| S-600918 300 mg | Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points | 60 Participants |
| Placebo | Number of Responders Defined as Participants With an Increase in LCQ of ≥ 1.3 Points | 48 Participants |
Secondary
Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-600918 50 mg | Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment | -54.43 percentage change |
| S-600918 150 mg | Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment | -53.17 percentage change |
| S-600918 300 mg | Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment | -65.48 percentage change |
| Placebo | Percent Change in Number of Coughs Per Hour While Asleep Following 4 Weeks of Study Treatment | -52.73 percentage change |
Secondary
Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment
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.
Time frame: Baseline to Week 4
Population: Full Analysis Set included all randomized participants who received at least 1 dose of study drug and who had cough monitor assessment at both baseline and at least 1 visit after initiation of study drug administration. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure at the specified timeframe.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| S-600918 50 mg | Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment | -55.77 percentage change |
| S-600918 150 mg | Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment | -61.75 percentage change |
| S-600918 300 mg | Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment | -66.33 percentage change |
| Placebo | Percent Change in Number of Coughs Per Hour While Awake Following 4 Weeks of Study Treatment | -60.31 percentage change |