Chronic Cough
Conditions
Brief summary
This estimation study (no hypotheses) will evaluate the safety, tolerability, and efficacy of gefapixant (MK-7264) in Japanese adult participants with unexplained or refractory chronic cough.
Interventions
DRUGGefapixant 45 mg
Gefapixant 45 mg (film-coated tablet) to be administered orally BID
DRUGPlacebo
Placebo (film-coated tablet) matching gefapixant to be 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
Japanese adult participants with refractory or unexplained chronic cough will be randomized to 1 of 2 treatment groups: gefapixant 45 mg twice daily (BID), or placebo BID.
Eligibility
Sex/Gender
ALL
Age
20 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 ≥ 1 year and a diagnosis of refractory chronic cough or unexplained chronic cough. * For female participants, 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 a pack-year history \>20 pack-years * Has a history of upper or lower 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 a history of malignancy ≤5 years * Has a screening systolic blood pressure \>160 millimeters of mercury (mmHg) or a diastolic blood pressure \>90 mm Hg * Has a history of cutaneous adverse drug reaction to sulfonamides with or without systemic symptoms or history of anaphylaxis to sulfonamides * Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence * 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 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 an Adverse Event | Up to 6 weeks | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | Up to 4 weeks | An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline at Week 4 in Log-transformed 24-hour Coughs Per Hour | Baseline and Week 4 | Cough frequency will be evaluated using a digital recording device which records sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. Change from baseline in log-transformed 24-hour coughs per hour = log (24-hour coughs per hour at post-baseline) - log (24-hour coughs per hour at baseline). The denominators may be different if the recording period is actually \<24 hours but ≥20 hours). |
| Change From Baseline at Week 4 in Log-transformed Awake Coughs Per Hour | Baseline and Week 4 | Change from baseline at Week 4 in awake coughs per hour is the average hourly cough frequency (based on sound recordings) during the 24-hour monitoring period while the participant is awake. Change from baseline in log-transformed awake coughs per hour = log (awake coughs per hour at post-baseline) - log (awake coughs per hour at baseline) for the monitoring period the participant is awake. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant 45 mg Participants received a gefapixant 45 mg film-coated tablet twice daily for 28 days. | 11 |
| Placebo Participants received a film-coated placebo tablet matching gefapixant twice daily for 28 days. | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Gefapixant 45 mg | Total | Placebo |
|---|---|---|---|
| 24-hour cough frequency | 40.1 coughs/hour STANDARD_DEVIATION 86.7 | 31.1 coughs/hour STANDARD_DEVIATION 60.9 | 22.9 coughs/hour STANDARD_DEVIATION 20.5 |
| Age, Continuous | 54.5 Years STANDARD_DEVIATION 15.7 | 55.9 Years STANDARD_DEVIATION 13.5 | 57.2 Years STANDARD_DEVIATION 11.7 |
| Awake cough frequency | 49.0 coughs/hour STANDARD_DEVIATION 103 | 37.7 coughs/hour STANDARD_DEVIATION 71.9 | 27.3 coughs/hour STANDARD_DEVIATION 21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants | 23 Participants | 12 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 |
| Region of Enrollment Japan | 11 Participants | 23 Participants | 12 Participants |
| Sex: Female, Male Female | 8 Participants | 17 Participants | 9 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 9 / 11 | 2 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to 4 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gefapixant 45 mg | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 1 Participants |
| Placebo | Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to 6 weeks
Population: All randomized participants who received at least one dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Gefapixant 45 mg | Number of Participants Who Experienced an Adverse Event | 9 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event | 2 Participants |
Secondary
Change From Baseline at Week 4 in Log-transformed 24-hour Coughs Per Hour
Cough frequency will be evaluated using a digital recording device which records sounds from the lungs and trachea through a chest contact sensor, as well as ambient sounds through a lapel microphone. Change from baseline in log-transformed 24-hour coughs per hour = log (24-hour coughs per hour at post-baseline) - log (24-hour coughs per hour at baseline). The denominators may be different if the recording period is actually \<24 hours but ≥20 hours).
Time frame: Baseline and Week 4
Population: All randomized participants who have taken at least one dose of study medication and provided at least one baseline and one post-baseline 24-hour cough observations during the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant 45 mg | Change From Baseline at Week 4 in Log-transformed 24-hour Coughs Per Hour | -0.23 Coughs/hour | Standard Error 0.39 |
| Placebo | Change From Baseline at Week 4 in Log-transformed 24-hour Coughs Per Hour | -1.02 Coughs/hour | Standard Error 0.38 |
95% CI: [-0.34, 1.93]
Secondary
Change From Baseline at Week 4 in Log-transformed Awake Coughs Per Hour
Change from baseline at Week 4 in awake coughs per hour is the average hourly cough frequency (based on sound recordings) during the 24-hour monitoring period while the participant is awake. Change from baseline in log-transformed awake coughs per hour = log (awake coughs per hour at post-baseline) - log (awake coughs per hour at baseline) for the monitoring period the participant is awake.
Time frame: Baseline and Week 4
Population: All randomized participants who have taken at least one dose of study medication and provided at least one baseline and one post-baseline awake cough observations during the treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant 45 mg | Change From Baseline at Week 4 in Log-transformed Awake Coughs Per Hour | -0.20 Coughs/hour | Standard Error 0.38 |
| Placebo | Change From Baseline at Week 4 in Log-transformed Awake Coughs Per Hour | -0.97 Coughs/hour | Standard Error 0.37 |
95% CI: [-0.35, 1.88]