Chronic Cough
Conditions
Keywords
Cough, Respiration disorders, Respiratory tract diseases, Signs and symptoms, respiratory, Signs and symptoms
Brief summary
The purpose of this study is to evaluate the efficacy and safety of gefapixant in participants with recent onset chronic cough (duration \>8 weeks after onset of cough symptoms) for \<12 months and a diagnosis of refractory or unexplained chronic cough. The primary hypothesis is that gefapixant is superior to placebo in improving cough-related quality of life measured as change from baseline in the Leicester Cough Questionnaire (LCQ) total score at Week 12.
Interventions
DRUGGefapixant
Administered twice daily as an oral tablet of 45 mg
DRUGPlacebo
Administered twice daily as a placebo oral tablet matching gefapixant
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chest radiograph or CT thorax (within 1 year 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 subinvestigator * Has chronic cough (defined as duration of \>8 weeks after onset of cough symptoms) for \<12 months prior to the screening visit (\<14 months after onset of cough symptoms) * Has a diagnosis of refractory chronic cough or unexplained chronic cough * Female participants are not pregnant, not breastfeeding, not of childbearing potential, or agree to follow contraceptive guidance
Exclusion criteria
* Is a current smoker * Has given up smoking within 12 months of screening * Is a former smoker with a smoking history greater than 20 pack-years (1 pack of 20 cigarettes per day for 20 years) * Has a history of respiratory tract infection or recent change in pulmonary status within 4 weeks of screening * Has a history of chronic bronchitis, defined as cough that produces \>1 tablespoon of phlegm, that occurs every day for at least 3 months in a row * Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or cervical cancer * Is a user of recreational or illicit drugs or a recent history (within the last year) of drug or alcohol abuse * Has a history of anaphylaxis or cutaneous adverse drug reaction to sulfonamide-containing drugs * Has a known allergy to gefapixant or its excipients * Has donated or lost ≥1 unit (\ 300 mL) of blood within 8 weeks prior to first dose of gefapixant * Has previously received gefapixant * Is currently participating or has participated in an interventional clinical study within 30 days of participating in this current study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | Baseline, Week 12 | Participants will be asked to complete the LCQ to assess the impact of their cough severity on health related quality of life (HRQoL) over the past 2 weeks. The LCQ is a 19-item, cough-specific HRQoL questionnaire. Each item on the LCQ assesses symptoms using a 7-point scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 (lowest total score) to 21 (highest total score). Higher scores indicate better HRQoL. The change from baseline in LCQ total score is calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12 | Baseline, Week 12 | Participants will be asked to complete the VAS questionnaire to assess the severity of their cough over the past 24-hours. The Cough Severity VAS is a single-item questionnaire asking the participant to rate the severity of their cough on a 100-point scale ranging from 0 (No Cough) to 100 (Extremely Severe Cough). Higher scores indicate greater severity of cough. The change from baseline in VAS score is calculated. |
| Percentage of Participants With One or More Adverse Events (AEs) | Up to approximately 14 weeks | An AE is defined as 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. The percentage of participants with one or more AEs is presented. |
| Percentage of Participants Who Discontinue Study Drug Due to an AE | Up to approximately 12 weeks | An AE is defined as 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. The percentage of participants who discontinue study drug due to an AE is presented. |
Countries
Canada, Colombia, Germany, Guatemala, Peru, Poland, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant Participants receive gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks. | 208 |
| Placebo Participants receive placebo matching gefapixant, administered as an oral tablet twice daily for 12 weeks. | 211 |
| Total | 419 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 11 | 5 |
Baseline characteristics
| Characteristic | Gefapixant | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 52.6 Years STANDARD_DEVIATION 13.8 | 52.5 Years STANDARD_DEVIATION 13.7 | 52.6 Years STANDARD_DEVIATION 13.7 |
| Baseline Leicester Cough Questionnaire (LCQ) | 10.8 Scores on a scale STANDARD_DEVIATION 3.1 | 11.3 Scores on a scale STANDARD_DEVIATION 2.8 | 11.0 Scores on a scale STANDARD_DEVIATION 3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 71 Participants | 76 Participants | 147 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 136 Participants | 134 Participants | 270 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 22 Participants | 28 Participants | 50 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 29 Participants | 29 Participants | 58 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 | 151 Participants | 152 Participants | 303 Participants |
| Sex: Female, Male Female | 136 Participants | 135 Participants | 271 Participants |
| Sex: Female, Male Male | 72 Participants | 76 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 208 | 1 / 211 |
| other Total, other adverse events | 105 / 206 | 22 / 209 |
| serious Total, serious adverse events | 3 / 206 | 4 / 209 |
Outcome results
Primary
Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12
Participants will be asked to complete the LCQ to assess the impact of their cough severity on health related quality of life (HRQoL) over the past 2 weeks. The LCQ is a 19-item, cough-specific HRQoL questionnaire. Each item on the LCQ assesses symptoms using a 7-point scale ranging from 1 to 7. The LCQ contains three domains on physical, psychological, and social functioning, and each domain score is calculated as the mean score of the items (range: 1 to 7) within the domain. The LCQ total score is the sum of the 3 domains, with a range from 3 (lowest total score) to 21 (highest total score). Higher scores indicate better HRQoL. The change from baseline in LCQ total score is calculated.
Time frame: Baseline, Week 12
Population: All randomized participants who have taken at least one dose of study intervention, and had LCQ total score values at both baseline and week 12. Participants were analyzed in the group as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | 4.34 Scores on a Scale |
| Placebo | Change From Baseline in the Leicester Cough Questionnaire (LCQ) Total Score at Week 12 | 3.59 Scores on a Scale |
p-value: 0.03495% CI: [0.06, 1.44]Longitudinal ANCOVA
Secondary
Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12
Participants will be asked to complete the VAS questionnaire to assess the severity of their cough over the past 24-hours. The Cough Severity VAS is a single-item questionnaire asking the participant to rate the severity of their cough on a 100-point scale ranging from 0 (No Cough) to 100 (Extremely Severe Cough). Higher scores indicate greater severity of cough. The change from baseline in VAS score is calculated.
Time frame: Baseline, Week 12
Population: All randomized participants who have taken at least one dose of study intervention, and had VAS total score values at both baseline and week 12. Participants were analyzed in the group as randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gefapixant | Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12 | -31.79 Scores on a Scale |
| Placebo | Change From Baseline in the Cough Severity Visual Analog Scale (VAS) Score at Week 12 | -24.87 Scores on a Scale |
p-value: 0.00695% CI: [-11.88, -1.97]Longitudinal ANCOVA
Secondary
Percentage of Participants Who Discontinue Study Drug Due to an AE
An AE is defined as 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. The percentage of participants who discontinue study drug due to an AE is presented.
Time frame: Up to approximately 12 weeks
Population: All randomized participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant | Percentage of Participants Who Discontinue Study Drug Due to an AE | 11.2 Percentage of Participants |
| Placebo | Percentage of Participants Who Discontinue Study Drug Due to an AE | 1.9 Percentage of Participants |
Secondary
Percentage of Participants With One or More Adverse Events (AEs)
An AE is defined as 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. The percentage of participants with one or more AEs is presented.
Time frame: Up to approximately 14 weeks
Population: All randomized participants who received at least 1 dose of study intervention. Participants were analyzed in the group as treated.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gefapixant | Percentage of Participants With One or More Adverse Events (AEs) | 65.5 Percentage of Participants |
| Placebo | Percentage of Participants With One or More Adverse Events (AEs) | 43.1 Percentage of Participants |