Chronic Cough
Conditions
Brief summary
The primary objective of this study is to evaluate the safety of two doses of gefapixant (MK-7264) in Japanese adult participants with refractory or unexplained chronic cough.
Interventions
DRUGGefapixant
Gefapixant 15 mg or 45 mg tablet administered orally BID
DRUGPlacebo
Placebo matched to gefapixant 15 mg or 45 mg administered orally BID
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chest radiograph or computed tomography scan of the thorax 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. * Chronic cough for ≥ 4 months and a diagnosis of refractory or unexplained chronic cough. * Persistent cough, despite treatment in accordance with the latest guideline of cough from the Japanese Respiratory Society, cough is a burden to the participant, and needs further treatment. * If female, is not pregnant, not breast-feeding, and either is not a woman of childbearing potential or agrees to follow the contraceptive guidance.
Exclusion criteria
* Current smoker, or has given up smoking within 12 months of Screening. * History of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status. * Has a history of chronic bronchitis. * Current use of an angiotensin converting enzyme inhibitor (ACEI) or has taken an ACEI within 3 months of Screening. * Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m\^2 OR ≥30 mL/min/1.73 m\^2 and \<50 mL/min/1.73 m\^2 at Visit 1 with unstable renal function (defined as a ≥50% increase of serum creatinine compared to a value obtained at least 6 months prior to Visit 1). * History of malignancy ≤ 5 years. * User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence. * Systolic blood pressure \>160 mm Hg or a diastolic blood pressure \>90 mm Hg at Screening. * History of cutaneous adverse drug reaction to sulfonamide antibiotics or other sulfonamide-containing drugs. * Known allergy/sensitivity or contraindication to gefapixant. * Donated or lost ≥1 unit of blood within 8 weeks prior to the first dose of gefapixant. * Previously received gefapixant or is currently participating in or has participated in an interventional clinical study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced at Least One Adverse Event (AE) | 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 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 |
|---|---|---|
| Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | Baseline, Week 12 | The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model. |
| Change From Baseline in LCQ Total Score | Baseline, up to 52 Weeks | The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model at weeks 4, 8, 12, 24, 38 and 52 of treatment. |
| Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Baseline, Up to 52 Weeks | The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. 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 weeks 4, 8, 12, 24, 38 and 52 of treatment. |
Countries
Japan
Participant flow
Pre-assignment details
A total of 175 participants were originally enrolled in the study. 6 participants at one site were excluded from all analyses, including disposition, due to good clinical practice (GCP) noncompliance at the study site.
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant 15 mg BID Participants received a gefapixant 15 mg tablet and a placebo tablet to match gefapixant 45 mg twice daily (BID) for 52 weeks | 84 |
| Gefapixant 45 mg BID Participants received a gefapixant 45 mg tablet and a placebo tablet to match gefapixant 15 mg BID for 52 weeks | 85 |
| Total | 169 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 6 |
Baseline characteristics
| Characteristic | Gefapixant 45 mg BID | Total | Gefapixant 15 mg BID |
|---|---|---|---|
| Age, Continuous | 57.6 Years STANDARD_DEVIATION 15.8 | 57.9 Years STANDARD_DEVIATION 15 | 58.2 Years STANDARD_DEVIATION 14.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 169 Participants | 84 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 85 Participants | 169 Participants | 84 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 51 Participants | 106 Participants | 55 Participants |
| Sex: Female, Male Male | 34 Participants | 63 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 84 | 0 / 85 |
| other Total, other adverse events | 73 / 84 | 76 / 85 |
| serious Total, serious adverse events | 2 / 84 | 10 / 85 |
Outcome results
Primary
Number of Participants Who Discontinued 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 treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gefapixant 15 mg BID | Number of Participants Who Discontinued Study Drug Due to an AE | 6 Participants |
| Gefapixant 45 mg | Number of Participants Who Discontinued Study Drug Due to an AE | 17 Participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event (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 54 Weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gefapixant 15 mg BID | Number of Participants Who Experienced at Least One Adverse Event (AE) | 79 Participants |
| Gefapixant 45 mg | Number of Participants Who Experienced at Least One Adverse Event (AE) | 82 Participants |
Secondary
Change From Baseline in LCQ Total Score
The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model at weeks 4, 8, 12, 24, 38 and 52 of treatment.
Time frame: Baseline, up to 52 Weeks
Population: All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 4 | 0.9 Scores on a Scale |
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 8 | 1.5 Scores on a Scale |
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 12 | 1.4 Scores on a Scale |
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 24 | 1.6 Scores on a Scale |
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 38 | 1.8 Scores on a Scale |
| Gefapixant 15 mg BID | Change From Baseline in LCQ Total Score | Week 52 | 2.3 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 38 | 1.2 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 4 | 0.8 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 24 | 1.1 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 8 | 1.2 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 52 | 1.5 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in LCQ Total Score | Week 12 | 0.9 Scores on a Scale |
Secondary
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12
The LCQ is a 19-item cough-specific health-related quality of life (HRQoL) questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. Higher scores indicate better HRQoL. The least squares mean of the change from baseline is based on a longitudinal analysis of covariance (ANCOVA) model.
Time frame: Baseline, Week 12
Population: All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant 15 mg BID | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | 1.4 Scores on a Scale |
| Gefapixant 45 mg | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | 0.9 Scores on a Scale |
Secondary
Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score
The LCQ is a 19-item cough-specific HRQoL questionnaire which contains three domains (physical, psychological and social), calculated as a mean score for each domain ranging from 1 to 7 and total score ranging from 3 to 21. Each item on the LCQ is assessed using a 7-point Likert scale ranging from 1 to 7. 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 weeks 4, 8, 12, 24, 38 and 52 of treatment.
Time frame: Baseline, Up to 52 Weeks
Population: All randomized participants who have taken at least one dose of study treatment and provided at least one baseline and one post-baseline endpoint observations during the treatment period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 4 | 38.1 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 8 | 43.4 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 12 | 48.2 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 24 | 53.7 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 38 | 56.1 Percentage of Participants |
| Gefapixant 15 mg BID | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 52 | 58.8 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 38 | 44.9 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 4 | 36.5 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 24 | 45.7 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 8 | 43.2 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 52 | 46.8 Percentage of Participants |
| Gefapixant 45 mg | Percentage of Participants With a ≥1.3 Point Change From Baseline in the LCQ Total Score | Week 12 | 40.7 Percentage of Participants |