Refractory Chronic Cough
Conditions
Brief summary
This was an 8-week randomized, parallel, double-blind, placebo-controlled study of gefapixant (AF-219) in participants with refractory chronic cough.
Interventions
DRUGGefapixant
Gefapixant tablets administered by mouth twice daily for 8 weeks
Matching placebo to gefapixant tablets administered by mouth twice daily for 8 weeks
Sponsors
Afferent Pharmaceuticals, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
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 80 Years
Healthy volunteers
No
Inclusion criteria
* Women and Men between 18 and 80 years of age inclusive * Have refractory chronic cough * Women of child-bearing potential must use 2 forms of acceptable birth control * Have provided written informed consent. * Are willing and able to comply with all aspects of the protocol.
Exclusion criteria
* Current smoker * Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) \< 60% * History of upper respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline * History of opioid use within 1 week of the Baseline Visit * Body mass index (BMI) \<18 kg/m2 or ≥ 40 kg/m2 * History of concurrent malignancy or recurrence of malignancy within 2 years prior to Screening (not including participants with \<3 excised basal cell carcinomas) * Screening systolic blood pressure (SBP) \>160 mm Hg or a diastolic blood pressure (DBP) \>90 mm Hg * Significantly abnormal laboratory tests at Screening * Clinically significant abnormal electrocardiogram (ECG) * Pregnant or Breastfeeding * Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the Investigator or Sponsor, would make the participants inappropriate for entry into this trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment. | Baseline and Week 8 (Day 56) | Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0, and after administration of the study drug on Day 56. The cough frequency is the coughs/hr over each 24 hour period. An independent cough monitoring core lab provided documentation of the time of each cough event over each 24-hour period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency. |
Countries
United States
Participant flow
Recruitment details
Male and female participants with treatment-refractory chronic cough were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Gefapixant 15 mg Twice Daily Two 7.5 mg gefapixant tablets administered by mouth twice daily for 8 weeks | 8 |
| Gefapixant 30 mg Twice Daily Four 7.5 mg gefapixant tablets administered by mouth twice daily for 8 weeks | 5 |
| Gefapixant 50 mg Twice Daily One 50 mg gefapixant tablet administered by mouth twice daily for 8 weeks | 6 |
| Placebo to Match Gefapixant Matching placebo tablets administered by mouth twice daily for 8 weeks | 4 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Gefapixant 15 mg Twice Daily | Gefapixant 30 mg Twice Daily | Gefapixant 50 mg Twice Daily | Placebo to Match Gefapixant | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.30 Years STANDARD_DEVIATION 10.39 | 66.60 Years STANDARD_DEVIATION 7.3 | 62.70 Years STANDARD_DEVIATION 11.04 | 63.50 Years STANDARD_DEVIATION 2.38 | 62.80 Years STANDARD_DEVIATION 8.85 |
| Cough Frequency | 57.6 Coughs/hour STANDARD_DEVIATION 35.98 | 42.7 Coughs/hour STANDARD_DEVIATION 21.22 | 41.0 Coughs/hour STANDARD_DEVIATION 29.98 | 60.4 Coughs/hour STANDARD_DEVIATION 38.84 | 50.6 Coughs/hour STANDARD_DEVIATION 30.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 5 Participants | 6 Participants | 3 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 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 | 8 Participants | 5 Participants | 5 Participants | 4 Participants | 22 Participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 5 Participants | 3 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
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 / 4 | 0 / 8 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 4 / 4 | 5 / 8 | 4 / 5 | 6 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 | 1 / 5 | 0 / 6 |
Outcome results
Primary
Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment.
Cough monitoring was conducted for 24 hours while awake, at pre-dose on Day 0, and after administration of the study drug on Day 56. The cough frequency is the coughs/hr over each 24 hour period. An independent cough monitoring core lab provided documentation of the time of each cough event over each 24-hour period. A negative change indicates a decrease in cough frequency, while a positive change indicates an increase in cough frequency.
Time frame: Baseline and Week 8 (Day 56)
Population: All randomized participants who took at least 1 dose of study medication and provided at least one baseline and at least one post-dose observation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gefapixant 15 mg Twice Daily | Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment. | -7.5 Coughs/hour | Standard Deviation 40.58 |
| Gefapixant 30 mg Twice Daily | Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment. | -16.9 Coughs/hour | Standard Deviation 13.68 |
| Gefapixant 50 mg Twice Daily | Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment. | -18.5 Coughs/hour | Standard Deviation 26.88 |
| Placebo to Match Gefapixant | Change From Baseline in Awake Cough Frequency After 8 Weeks of Treatment. | 0.3 Coughs/hour | Standard Deviation 24.96 |
Comparison: Least squares mean (LSM) difference: Mixed effect repeated measures model (MMRM) uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-2.08, 0.96]
Comparison: LSM difference: MMRM uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-2.34, 0.92]
Comparison: LSM difference: MMRM uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-2.99, 0.3]
Comparison: Estimated Percentage Change: MMRM uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-87.5, 162.3]
Comparison: Estimated Percentage Change: MMRM uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-90.3, 151.1]
Comparison: Estimated Percentage Change: MMRM uses the change from baseline as the dependent variable, and includes the treatment group, visit day, and the interaction between treatment and visit as fixed factors, and baseline as a covariate.95% CI: [-95, 34.7]