|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Medical condition in easily understood language
|Diseases [C] - Respiratory Tract Diseases [C08]
|E.1.2 Medical condition or disease under investigation
|System Organ Class
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|- To evaluate the efficacy of MK-7264 in reducing cough frequency as measured over a 24-hour period
- To evaluate the safety and tolerability of MK-7264
|Secondary objectives of the trial
|- To evaluate the efficacy of MK-7264 in reducing cough frequency as measured while awake during a 24-hour period
- To evaluate the efficacy of MK-7264 based on the proportion of participants with a clinically significant reduction from baseline in 24-hour coughs per hour
- To evaluate the efficacy of MK-7264 in improving self-rated cough severity
- To evaluate the ability of MK-7264 to provide a clinically significant improvement in cough specific quality of life
|Trial contains a sub-study
|Full title, date and version of each sub-study and their related objectives
|Merck will conduct Future Biomedical Research on DNA. Such research is for biomarker testing to address emergent questions not described elsewhere in the protocol (as part of the main trial) and will only be conducted on specimens from appropriately consented subjects. The objective of collecting specimens for Future Biomedical Research is to explore and identify biomarkers that inform the scientific understanding of diseases and/or their therapeutic treatments. The overarching goal is to use such information to develop safer, more effective drugs, and/or to ensure that subjects receive the correct dose of the correct drug at the correct time.
|Principal inclusion criteria
|1. 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.
2. Have chronic cough for ≥1 year and a diagnosis of refractory chronic cough or unexplained chronic cough.
3. Have a score of ≥40 mm on the Cough Severity VAS at both the Screening and Baseline visits.
4. Participant is Male or Female at least 18 years of age at the time of signing the informed consent.
5. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
b. A WOCBP who agrees to follow the contraceptive guidance from the time of signing the informed consent through at least 14 days after the last dose of study intervention.
6. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
7. The participant is willing and able to comply with all aspects of the protocol, including demonstrating an ability to follow study procedures (including use of the digital cough recording device and completion of the Cough Severity VAS, CSD, LCQ, and other protocol questionnaires) to the satisfaction of the investigator/qualified designee prior to randomization.
|Principal exclusion criteria
|1. Current smoker.
2. Individuals who have given up smoking within 12 months of Screening/Visit 1.
3. Former smokers with a pack/year history greater than 20 pack-years.
4. Forced expiratory volume in 1 second (FEV1)/ forced vital capacity (FVC) ratio <60% (spirometry performed within the past year is acceptable if the investigator confirms that spirometry was done during a period where the participant was clinically stable, eg, not during an upper respiratory infection).
5. History of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status within 4 weeks of Screening/Visit 1.
6. History of chronic bronchitis, defined as a cough that produces a clinically significant amount of sputum (greater than approximately 1 tablespoon of phlegm) that occurs every day for at least 3 months in a row, with those periods occurring at least 2 years in a row.
7. Individuals who are currently taking an angiotensin converting enzyme inhibitor or have taken an angiotensin converting enzyme inhibitor within 3 months of Screening/Visit 1.
8. Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at Screening OR eGFR ≥30 mL/min/1.73 m2 and <50 mL/min/1.73 m2 at Screening with unstable renal function (defined as a ≥50% increase of serum creatinine compared to a value obtained at least 6 months prior to Screening/Visit 1).
9. 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.
10. Is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence.
11. Screening systolic blood pressure >160 mm Hg or a diastolic blood pressure >90 mm Hg.
12. History of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs.
13. Has a known allergy/sensitivity or contraindication to MK-7264 or its excipients.
14. Has donated or lost ≥1 unit of blood (approximately 300 mL) within 8 weeks prior to the first dose of MK-7264.
15. A WOCBP who has a positive urine pregnancy test at Visit 1. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
16. Requiring treatment with a therapy that does not adhere to the guidance parameters specified in the Protocol.
17. Has previously received MK-7264.
18. Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 30 days of participating in this current study.
19. Significantly abnormal laboratory tests at Screening.
20. Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study intervention administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study.
21. Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this study.
|E.5 End points
|Primary end point(s)
|- 24-hour coughs per hour at Week 12
- Number of participants experiencing an AE
- Number of participants discontinuing study intervention due to an AE
|Timepoint(s) of evaluation of this end point
|- Week 12 (Efficacy)
- Throughout study (Safety)
|Secondary end point(s)
|- Awake coughs per hour at Week 12
- Proportion of participants with a ≥30% reduction from baseline in 24-hour coughs per hour at Week 12
- Proportion of participants with a ≥1.3 point reduction from baseline in mean weekly Cough Severity Diary (CSD) total score at Week 12
- Proportion of participants with a ≥2.7 point reduction from baseline in mean weekly CSD total score at Week 12
- Proportion of participants with a ≥30 mm reduction from baseline in Cough Severity Visual Analog Scale (VAS) score at Week 12
- Proportion of participants with a ≥1.3 point increase from baseline in Leicester Cough Questionnaire (LCQ) total score at Week 12
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Korea, Republic of
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days