Efficacy of Gefapixant in Women with Chronic Cough and Stress Urinary Incontinence

Phase 1

Conditions: Chronic Cough and Stress Urinary Incontinence
MedDRA version: 21.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855
MedDRA version: 20.0 Level: PT Classification code 10066218 Term: Stress urinary incontinence System Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2019-002321-29-ES

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 380

Inclusion Criteria

Chronic Cough
1. Has a 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 subinvestigator.
2. Has a chronic cough (defined as duration of >8 weeks after onset of symptoms) for =12 months.
3. Has a diagnosis of refractory chronic cough or unexplained chronic cough.
4. Meet a certain cough severity score at certain study visits.
Stress Urinary Incontinence
5. Has symptoms of SUI, defined as involuntary loss of urine on effort, physical exertion, or on sneezing or coughing, for = 3 months.
6. Has pure or predominant SUI, based on certain criteria
7. Has a history of cough-induced SUI, based on certain criteria.
8. Meets a certain number of cough-induced SUI episodes.
9. Has a positive cough stress test at Screening/Visit 1.
Demographics
10. Is female, 18 years of age or older, at the time of signing the informed consent.
11. Has a body mass index of = 40 kg/m2.
Female Participants
Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
OR
- Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 2 weeks (14 days) after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
Informed Consent
13. Provides written informed consent for the study (or legally acceptable representative, if applicable). The participant may also provide consent for future biomedical research.
However, the participant may participate in the study without participating in future biomedical research.
Study Participation
14. Demonstrates compliance with diary completion requirements.
15. Is willing and able to comply with all aspects of the protocol, including agreeing not to smoke during the study and demonstrating an ability to follow study procedures (including completion of the I-QoL, CSD, and Cough Severity VAS) to the satisfaction of the investigator/qualified designee prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 190
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 190

Exclusion Criteria

1. Is a current smoker
2. Has given up smoking within 12 months of Screening/Visit 1
3. Is a former smoker with a smoking history greater than 20 pack-years
4. Has a FEV1/ FVC ratio <60%
5. Has a history of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status within 4 weeks of Screening/Visit 1
6. Has a history of chronic bronchitis, defined as a cough that produces a clinically significant amount of sputum that occurs every day for at least 3 months in a row, with those periods occurring at least 2 years in a row
7. Has a history of surgery to treat SUI within 1 year of the Screening/Visit 1
8. Has a history of other specialized treatments for SUI, including intravesical balloon or urethral bulking agent therapy
9. Has a pessary or other external incontinence device currently or within 1 month of the Screening/Visit 1
10. Has a history of Grade 3 or higher pelvic organ prolapse previously documented or diagnosed on screening examination
11. Has a neurogenic bladder
12. Has unexplained hematuria or has dysuria at Screening/Visit 1
13. Has a history of adult nocturnal incontinence
14. Has a history of continuous urine leakage within 1 month of the Screening/Visit 1
15. Has a history of interstitial cystitis
16. Has a history of clinically significant neurological disease or injury that could affect the lower urinary tract or its nerve supply
17. Has active or recurrent urinary tract infection
18. Has a history of having a permanent urinary catheter or any urinary
catheterization within 3 months of the Screening/ Visit 1
19. Has an eGFR <30 mL/min/1.73 m2 at Screening/Visit 1 OR eGFR =30 mL/min/1.73 m2 and <50 mL/min/1.73 m2 at Screening/Visit 1 with unstable renal function
20. Has a history of malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
21. Is, at the time of signing the informed consent, a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence
22. Has a history of anaphylaxis or cutaneous adverse drug reaction to sulfonamide antibiotics or other sulfonamide-containing drugs.
23. Has a known allergy/sensitivity or contraindication to gefapixant or its excipients
24. Has donated or lost =1 unit of blood within 8 weeks prior to the first dose of gefapixant
25. Is a WOCBP who has a positive urine pregnancy test at Screening/Visit 1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
26. Requires treatment with a therapy for chronic cough that does not adhere to the guidance parameters for concomitant medication
27. Is currently taking an angiotensin converting enzyme inhibitor or has taken an angiotensin converting enzyme inhibitor within 3 months of Screening/Visit 1
28. Requires the following pharmacologic therapies that may impact bladder function, which are not allowed from 2 weeks prior to Screening/Visit 1 through comple

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: 1. To evaluate the safety and tolerability of gefapixant compared to placebo in percent of participants with adverse events (AEs);Primary end point(s): 1. Percent change from baseline in average daily cough-induced stress urinary incontinence (SUI) episodes at Week 12;Timepoint(s) of evaluation of this end point: 1. Baseline, Week 12;Main Objective: 1. To evaluate the efficacy of gefapixant (MK-7264) in reducing the frequency of cough-induced stress urinary incontinence (SUI) episodes compared to placebo as determined by a participant Incontinence Diary, measured as percentage change from baseline in episodes of cough-induced SUI at Week 12

Secondary Outcome Measures

Name	Time	Method
<br> Secondary end point(s): 1. Percentage of participants with one or more adverse events (AEs)<br> 2. Percentage of participants who discontinue study drug due to an AE<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Up to ~Week 14<br> 2. Up to Week 12<br>