Chronic Cough
Conditions
Keywords
Cough, Urinary Incontinence, Stress, 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 improving symptoms of cough-induced stress urinary incontinence (SUI) in adult female participants with refractory or unexplained chronic cough. The primary hypothesis is that gefapixant is superior to placebo in reducing the frequency of cough-induced SUI episodes over 12 weeks.
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
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a chest radiograph or computed tomography scan of the thorax (within 5 years of Screening and after the onset of chronic cough) not demonstrating any abnormality considered to be significantly contributing to the chronic cough or any other lung disease * Has chronic cough (defined as duration of \>8 weeks after onset of cough symptoms) for ≥12 months * Has a diagnosis of refractory chronic cough or unexplained chronic cough * Has symptoms of SUI, defined as involuntary loss of urine on effort, physical exertion, or on sneezing or coughing, for ≥3 months * Is a female who is not pregnant, not breastfeeding, not of childbearing potential, or agrees 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 * Has a history of surgery to treat SUI within 1 year of screening * Has a history of other specialized treatments for SUI, including intravesical balloon or urethral bulking agent therapy * Has other external incontinence device currently or within 1 month of screening * Has a history of Grade 3 or higher pelvic organ prolapse previously documented or diagnosed on screening * Has a neurogenic bladder * Has a history of adult nocturnal incontinence * Has a history of continuous urine leakage within 1 month of screening * Has a history of interstitial cystitis * Has a history of neurological disease or injury * Has active or recurrent urinary tract infection * Has a history of having a permanent urinary catheter or any urinary catheterization within 3 months of screening * Has a history of malignancy ≤5 years prior to signing informed consent * Is a user of recreational or illicit drugs or a recent history (within the last year) of drug or alcohol abuse * 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 * Requires certain medications and/or other therapies that may impact their cough or bladder function * 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 |
|---|---|---|
| Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12 | Baseline and week 12 | Cough-induced SUI episodes were assessed using an event-driven electronic Incontinence Diary where the participant recorded the main cause of each urinary incontinence episode as coughing, another stress reason, or other cause. Episodes of incontinence were recorded for the week before baseline and treatment visit. Average daily cough induced SUI episodes were calculated as (sum of daily cough-induced SUI episodes in a week)/number of days recorded. The percent change from baseline in the average daily cough-induced SUI episodes to Week 12 are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events | Up to ~16 weeks | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an adverse event are presented. |
| Percentage of Participants Who Discontinued Study Intervention Due to AEs | Up to ~14 weeks | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study intervention due to an adverse event are presented. |
Countries
Argentina, Colombia, Germany, Guatemala, Israel, Peru, Russia, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Of the 376 randomized participants, 375 participants received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo administered as an oral tablet twice daily for 12 weeks. | 190 |
| Gefapixant Participants received gefapixant at a dose of 45 mg administered as an oral tablet twice daily for 12 weeks. | 186 |
| Total | 376 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 6 | 10 |
Baseline characteristics
| Characteristic | Placebo | Gefapixant | Total |
|---|---|---|---|
| Age, Continuous | 56.6 Years STANDARD_DEVIATION 11.3 | 56.2 Years STANDARD_DEVIATION 11.5 | 56.4 Years STANDARD_DEVIATION 11.4 |
| Baseline Mean Daily Cough-Induced Stress Urinary Incontinence Episodes, 7-day Average | 4.7 Number of episodes STANDARD_DEVIATION 4.1 | 4.7 Number of episodes STANDARD_DEVIATION 3 | 4.7 Number of episodes STANDARD_DEVIATION 3.6 |
| Baseline Mean Weekly Cough Severity in Visual Analog Scale (VAS) in mm | 69.5 VAS (mm) STANDARD_DEVIATION 15.6 | 69.3 VAS (mm) STANDARD_DEVIATION 15.8 | 69.4 VAS (mm) STANDARD_DEVIATION 15.7 |
| Body mass index | 29.7 kg/m^2 STANDARD_DEVIATION 4.4 | 29.7 kg/m^2 STANDARD_DEVIATION 4.8 | 29.7 kg/m^2 STANDARD_DEVIATION 4.6 |
| Duration of Chronic Cough | 5.1 Years STANDARD_DEVIATION 6.6 | 5.3 Years STANDARD_DEVIATION 6.5 | 5.2 Years STANDARD_DEVIATION 6.6 |
| Duration of Stress Urinary Incontinence (SUI) | 53.8 Months STANDARD_DEVIATION 80.8 | 43.4 Months STANDARD_DEVIATION 58.3 | 48.7 Months STANDARD_DEVIATION 70.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 79 Participants | 73 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 113 Participants | 224 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 159.6 centimeters STANDARD_DEVIATION 6.9 | 159.8 centimeters STANDARD_DEVIATION 7 | 159.7 centimeters STANDARD_DEVIATION 7 |
| Primary cough diagnosis Refractory Chronic Cough | 149 Participants | 141 Participants | 290 Participants |
| Primary cough diagnosis Unexplained Chronic Cough | 41 Participants | 45 Participants | 86 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 16 Participants | 34 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 26 Participants | 24 Participants | 50 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 | 143 Participants | 137 Participants | 280 Participants |
| Region Asia Pacific | 3 Participants | 3 Participants | 6 Participants |
| Region Europe | 102 Participants | 102 Participants | 204 Participants |
| Region North America | 11 Participants | 9 Participants | 20 Participants |
| Region Other | 74 Participants | 72 Participants | 146 Participants |
| Sex: Female, Male Female | 190 Participants | 186 Participants | 376 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 75.6 kilograms STANDARD_DEVIATION 13.1 | 75.9 kilograms STANDARD_DEVIATION 13.3 | 75.8 kilograms STANDARD_DEVIATION 13.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 190 | 0 / 186 |
| other Total, other adverse events | 12 / 190 | 104 / 185 |
| serious Total, serious adverse events | 2 / 190 | 3 / 185 |
Outcome results
Primary
Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12
Cough-induced SUI episodes were assessed using an event-driven electronic Incontinence Diary where the participant recorded the main cause of each urinary incontinence episode as coughing, another stress reason, or other cause. Episodes of incontinence were recorded for the week before baseline and treatment visit. Average daily cough induced SUI episodes were calculated as (sum of daily cough-induced SUI episodes in a week)/number of days recorded. The percent change from baseline in the average daily cough-induced SUI episodes to Week 12 are presented.
Time frame: Baseline and week 12
Population: All randomized participants who received at least 1 dose of study intervention and had incontinence frequency of at least 4 days in the 7-day period prior to the visit at Week 12.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12 | -41.09 Percent Change |
| Gefapixant | Percent Change From Baseline in Average Daily Cough-induced Stress Urinary Incontinence (SUI) Episodes at Week 12 | -52.78 Percent Change |
p-value: 0.00495% CI: [-19.67, -3.67]ANCOVA
Secondary
Percentage of Participants Who Discontinued Study Intervention Due to AEs
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study intervention due to an adverse event are presented.
Time frame: Up to ~14 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Who Discontinued Study Intervention Due to AEs | 1.1 Percentage of participants |
| Gefapixant | Percentage of Participants Who Discontinued Study Intervention Due to AEs | 7.0 Percentage of participants |
Secondary
Percentage of Participants With Adverse Events
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an adverse event are presented.
Time frame: Up to ~16 weeks
Population: All randomized participants who received at least one dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events | 37.4 Percentage of participants |
| Gefapixant | Percentage of Participants With Adverse Events | 69.7 Percentage of participants |