Chronic Cough
Conditions
Brief summary
The primary objectives of this study are to evaluate the efficacy of gefapixant (MK-7264) in reducing cough frequency as measured over a 24-hour period, and to determine the safety and tolerability of gefapixant. The primary hypothesis is that at least one dose of gefapixant is superior to placebo in reducing coughs per hour (over 24 hours) at Week 24.
Detailed description
This study will have a main 24-week treatment period and a 28-week extension period of treatment (total treatment period of 52 weeks). Participants at selected sites and countries who complete the main and extension study periods may consent to participate in an observational, 12-week, Off-treatment Durability Study Period. Any assessments conducted in the observational period will be exploratory.
Interventions
DRUGPlacebo
Placebo tablet administered orally BID
Gefapixant 15 mg tablet administered orally BID
Gefapixant 45 mg tablet administered orally BID
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Participants with refractory or unexplained chronic cough will be randomized to 1 of 3 treatment groups: gefapixant 45 mg twice daily (BID), gefapixant 15 mg BID, or placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chest radiograph or computed tomography scan of the thorax (within 5 years of Screening/Visit 1 and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other clinically significant lung disease in the opinion of the principal investigator or the sub-investigator * Has had chronic cough for at least 1 year with a diagnosis of refractory chronic cough or unexplained chronic cough * Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees to follow contraceptive guidance * Provides written informed consent and is willing and able to comply with the study protocol (including use of the digital cough recording device and completion of study questionnaires)
Exclusion criteria
* Is a current smoker or has given up smoking within 12 months of Screening, or is a former smoker with greater than 20 pack-years * Has a history of respiratory tract infection or recent clinically significant change in pulmonary status * Has a history of chronic bronchitis * Is currently taking an angiotensin converting enzyme inhibitor (ACEI), or has used an ACEI within 3 months of Screening * Has an estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2 at Screening OR an eGFR ≥30 mL/min/1.73 m\^2 and \<50 mL/min/1.73 m\^2 at Screening with unstable renal function * Has a history of malignancy ≤5 years * Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence * Has a history of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs * Has a known allergy/sensitivity or contraindication to gefapixant * Has donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant * Has previously received gefapixant * Currently participating in or has participated in an interventional clinical study within 30 days of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline | Baseline, Week 24 | 24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported. |
| Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up | Up to 54 Weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Number of Participants Who Discontinued a Study Drug Due to an AE | Up to 52 weeks | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 | Baseline, Week 24 | The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-1.3 point change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported. |
| Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline | Baseline, Week 24 | Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported. |
| Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 | Baseline, Week 24 | The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 (No Cough) to 100 (Extremely Severe Cough). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported. |
| Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24 | Baseline, Week 24 | The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-2.7 point change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported. |
| Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 | Baseline, Week 24 | The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented. |
| Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24 | Baseline, Week 24 | 24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≤-30% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented. |
Countries
Australia, Canada, China, Colombia, Czechia, Denmark, Germany, Guatemala, Hungary, Israel, Italy, Malaysia, New Zealand, Peru, Poland, South Africa, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
1317 participants were randomized to the 52-week treatment period, and 1314 participants received at least 1 dose of study intervention. After the main study, 122 participants continued in an optional Off-Treatment observational study period (no treatment).
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received dose-matched placebo tablets twice daily (BID) during the 24-week main study period and 28-week extension period. | 436 |
| Gefapixant 15 mg BID Participants received a gefapixant 15 mg tablet and placebo tablet to match gefapixant 45 mg BID during the 24-week main study period and 28-week extension period. | 442 |
| Gefapixant 45 mg BID Participants received a gefapixant 45 mg tablet and placebo tablet to match gefapixant 15 mg BID during the 24-week main study period and 28-week extension period. | 439 |
| Total | 1,317 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 12-Week Off-Treatment Durability Period | Other | 0 | 1 | 0 |
| 12-Week Off-Treatment Durability Period | Withdrawal by Subject | 1 | 0 | 0 |
| 52-week Treatment Period | Death | 0 | 1 | 0 |
| 52-week Treatment Period | Lost to Follow-up | 6 | 2 | 5 |
| 52-week Treatment Period | Other | 0 | 1 | 2 |
| 52-week Treatment Period | Physician Decision | 1 | 0 | 3 |
| 52-week Treatment Period | Screen Failure | 1 | 2 | 0 |
| 52-week Treatment Period | Withdrawal by Subject | 46 | 68 | 74 |
Baseline characteristics
| Characteristic | Placebo | Gefapixant 15 mg BID | Gefapixant 45 mg BID | Total |
|---|---|---|---|---|
| Age, Continuous | 58.4 Years STANDARD_DEVIATION 12.5 | 58.4 Years STANDARD_DEVIATION 11.3 | 57.8 Years STANDARD_DEVIATION 12.4 | 58.2 Years STANDARD_DEVIATION 12.1 |
| Baseline 24-Hour Coughs Per Hour | 27.45 Coughs/Hour STANDARD_DEVIATION 24.44 | 26.82 Coughs/Hour STANDARD_DEVIATION 21.25 | 26.84 Coughs/Hour STANDARD_DEVIATION 27.04 | 27.04 Coughs/Hour STANDARD_DEVIATION 24.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 85 Participants | 93 Participants | 89 Participants | 267 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 348 Participants | 347 Participants | 344 Participants | 1039 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 20 Participants | 28 Participants | 24 Participants | 72 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 14 Participants | 15 Participants | 44 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 14 Participants | 28 Participants |
| Race (NIH/OMB) More than one race | 36 Participants | 31 Participants | 37 Participants | 104 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 356 Participants | 358 Participants | 346 Participants | 1060 Participants |
| Sex: Female, Male Female | 326 Participants | 331 Participants | 329 Participants | 986 Participants |
| Sex: Female, Male Male | 110 Participants | 111 Participants | 110 Participants | 331 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 433 | 1 / 444 | 0 / 440 | 0 / 48 | 0 / 37 | 0 / 37 |
| other Total, other adverse events | 248 / 432 | 290 / 442 | 359 / 440 | 6 / 48 | 3 / 37 | 1 / 37 |
| serious Total, serious adverse events | 25 / 432 | 24 / 442 | 25 / 440 | 0 / 48 | 0 / 37 | 1 / 37 |
Outcome results
Primary
Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline
24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A longitudinal analysis of covariance (ANCOVA) model was applied to log-transformed cough data to determine geometric mean (GM) 24-hour coughs per hour at baseline and week 24. The GMR (Week 24 GM 24-hour coughs per hour divided by Baseline GM 24-hour coughs per hour) is reported.
Time frame: Baseline, Week 24
Population: All randomized participants who took at least 1 dose of study intervention, had available 24-hour cough data at baseline and at least one available post-baseline measurement during the treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline | 0.43 Ratio |
| Gefapixant 15 mg BID | Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline | 0.43 Ratio |
| Gefapixant 45 mg BID | Model-Based Geometric Mean Ratio (GMR) of 24-Hour Coughs Per Hour at Week 24/Baseline | 0.37 Ratio |
Comparison: Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e\*\*DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.p-value: 0.87595% CI: [-14.27, 14.02]ANCOVA
Comparison: ERR relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e\*\*DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.p-value: 0.03195% CI: [-26.07, -1.43]ANCOVA
Primary
Number of Participants Who Discontinued a Study Drug Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 52 weeks
Population: All randomized participants who received at least one dose of study intervention during the 52-week treatment period. Per protocol, participants in the optional off-treatment observational period were not included. 3 participants randomized to placebo group who took 1 or more incorrect dose(s) of study drug were counted in the higher dose group of gefapixant received: 2 participants were analyzed in the gefapixant 15 mg group and 1 was analyzed in the gefapixant 45 mg group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Discontinued a Study Drug Due to an AE | 25 Participants |
| Gefapixant 15 mg BID | Number of Participants Who Discontinued a Study Drug Due to an AE | 40 Participants |
| Gefapixant 45 mg BID | Number of Participants Who Discontinued a Study Drug Due to an AE | 100 Participants |
Primary
Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time frame: Up to 54 Weeks
Population: All randomized participants who received at least one dose of study intervention during the 52-week treatment period. Per protocol, participants in the optional off-treatment observational period were not included. 3 participants randomized to placebo group who took 1 or more incorrect dose(s) of study drug were counted in the higher dose group of gefapixant received: 2 participants were analyzed in the gefapixant 15 mg group and 1 was analyzed in the gefapixant 45 mg group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up | 349 Participants |
| Gefapixant 15 mg BID | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up | 373 Participants |
| Gefapixant 45 mg BID | Number of Participants Who Experienced At Least One Adverse Event (AE) During Treatment and Follow-up | 399 Participants |
Secondary
Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline
Awake coughs per hour was defined as the average hourly cough frequency while the participant is awake, based on a 24-hour interval of sound recordings using a digital recording device (cough monitor). ANCOVA model was applied to log-transformed cough data to determine GM of awake coughs per hour at baseline and week 24. The GMR (Week 24 GM awake coughs per hour divided by Baseline GM awake coughs per hour) is reported.
Time frame: Baseline, Week 24
Population: All randomized participants who took at least 1 dose of study intervention, had available awake 24-hour cough data at baseline and at least one available post-baseline measurement during the treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Placebo | Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline | 0.42 Ratio |
| Gefapixant 15 mg BID | Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline | 0.41 Ratio |
| Gefapixant 45 mg BID | Model-Based GMR of Awake Coughs Per Hour at Week 24/Baseline | 0.36 Ratio |
Comparison: Estimated relative reduction (ERR) relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e\*\*DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.p-value: 0.67795% CI: [-16.14, 12.12]ANCOVA
Comparison: ERR relative to Placebo (i.e. estimated percent change difference) was calculated by 100 (e\*\*DIFF -1), where e = exponent of difference; and DIFF= treatment difference in change from baseline at Week 24 based on log transformed data.p-value: 0.02295% CI: [-27.27, -2.5]ANCOVA
Secondary
Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24
The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-1.3 point change from baseline in CSD at Week 24 (or ≥1.3 point reduction from baseline) is reported.
Time frame: Baseline, Week 24
Population: All randomized participants who had taken at least 1 dose of study intervention, had available CSD data at baseline, and at least one available post-baseline measurement in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 | 69.1 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 | 74.8 Percentage of Participants |
| Gefapixant 45 mg BID | Percentage of Participants With ≤-1.3 Point Change From Baseline of Mean Weekly Cough Severity Diary (CSD) Total Score at Week 24 | 77.1 Percentage of Participants |
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.95% CI: [0.96, 1.83]
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.95% CI: [1.08, 2.09]
Secondary
Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24
The 7-item CSD was used to record participants' daily cough frequency, cough intensity, and disruption due to cough. Each item was rated on an 11-point scale ranging from 0 (best) to 10 (worst); the total daily CSD score was the sum of these seven item scores (Min=0, Max=70). Mean weekly CSD total score was defined as the average of the mean total daily scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-2.7 point change from baseline in CSD at Week 24 (or ≥2.7 point reduction from baseline) is reported.
Time frame: Baseline, Week 24
Population: All randomized participants who had taken at least 1 dose of study intervention, had available CSD data at baseline, and at least one available post-baseline measurement in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24 | 41.0 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24 | 46.6 Percentage of Participants |
| Gefapixant 45 mg BID | Percentage of Participants With ≤-2.7 Point Change From Baseline of Mean Weekly CSD Total Score at Week 24 | 55.2 Percentage of Participants |
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.95% CI: [0.93, 1.69]
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly CSD total score, and the interaction of baseline mean weekly CSD total score by visit as covariates.95% CI: [1.31, 2.39]
Secondary
Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24
The 19-item LCQ assessed the impact of chronic cough in three health-related quality of life (HRQoL) domains (physical, social and psychological). The LCQ is calculated as a mean score for each domain ranging from 1 to 7, with a total score ranging from 3 to 21. Higher scores indicate better HRQoL. A clinically meaningful improvement from baseline in HRQoL was defined as ≥1.3-point increase in the LCQ total score at Week 24. The percentage of participants (logistic regression model-based) with a ≥1.3-point increase in the LCQ total score at Week 24 is presented.
Time frame: Baseline, Week 24
Population: All randomized participants who had taken at least 1 dose of study intervention, had available LCQ data at baseline, and at least one available post-baseline measurement in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 | 70.1 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 | 75.9 Percentage of Participants |
| Gefapixant 45 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the Leicester Questionnaire (LCQ) Total Score at Week 24 | 76.8 Percentage of Participants |
p-value: 0.07795% CI: [0.97, 1.85]Regression, Logistic
p-value: 0.0495% CI: [1.02, 1.96]Regression, Logistic
Secondary
Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24
24-hour coughs per hour was defined as the average hourly cough frequency based on 24-hour sound recordings using a digital recording device (cough monitor). A clinically meaningful improvement from baseline is defined as a ≤-30% change (≥30% reduction) in 24-hour coughs per hour at week 24. The percentage of participants (logistic regression model-based) with a ≤ -30% change from baseline in 24-hour coughs per hour at Week 24 (≥30% reduction from baseline) is presented.
Time frame: Baseline, Week 24
Population: All randomized participants who took at least 1 dose of study intervention, had available 24-hour cough data at baseline and at least one available post-baseline measurement in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24 | 66.9 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24 | 67.4 Percentage of Participants |
| Gefapixant 45 mg BID | Percentage of Participants With a ≤-30% Change From Baseline in 24-hour Coughs Per Hour at Week 24 | 72.9 Percentage of Participants |
p-value: 0.87295% CI: [0.75, 1.4]Regression, Logistic
p-value: 0.08295% CI: [0.96, 1.83]Regression, Logistic
Secondary
Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24
The VAS is a single-item questionnaire with the response on a 100- point scale ranging from 0 (No Cough) to 100 (Extremely Severe Cough). Mean weekly VAS score was defined as the average of the VAS scores collected during the week prior to each visit. The percentage of participants (logistic regression model-based) with a ≤-30 mm change from baseline in cough severity VAS score at Week 24 is reported.
Time frame: Baseline, Week 24
Population: All randomized participants who had taken at least 1 dose of study intervention, had available VAS data at baseline, and at least one available post-baseline measurement in the treatment period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 | 40.9 Percentage of participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 | 51.4 Percentage of participants |
| Gefapixant 45 mg BID | Percentage of Participants With a ≤-30 Millimeter (mm) Change From Baseline in Cough Severity Visual Analog Scale (VAS) Score at Week 24 | 53.3 Percentage of participants |
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly VAS score, and the interaction of baseline mean weekly VAS score by visit as covariates.95% CI: [1.14, 2.05]
Comparison: Comparison based on a logistic regression model that included treatment, visit, treatment-by-visit interaction, gender, region, baseline mean weekly VAS score, and the interaction of baseline mean weekly VAS score by visit as covariates.95% CI: [1.23, 2.22]