Ensayos clínicos

Inclusion Criteria:

• 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 (note: sub-investigator must be a physician).
• Have chronic cough for ≥1 year and a diagnosis of refractory chronic cough or unexplained chronic cough as specified in Section 5.
• Have a score of ≥40 mm on the Cough Severity VAS at both the Screening and Baseline visits, as specified in Section 8.2.2.

Demographics

• Participant is Male or Female at least 18 years of age at the time of informed consent.

Female Participants

• A female participant is eligible to participate if she is not pregnant (Appendix 5), not breastfeeding, and at least 1 of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 5; OR
  •  A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 from the time of signing the informed consent through at least 14 days after the last dose of study intervention.

Informed Consent

• 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.

Study Participation

• 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.

Exclusion Criteria:

Medical Conditions

• Current smoker.
• Individuals who have given up smoking within 12 months of Screening/Visit 1.
• Former smokers with a pack/year history greater than 20 pack-years.
• 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; e.g., not during an upper respiratory infection).
• History of upper or lower respiratory tract infection or recent clinically significant change in pulmonary status within 4 weeks of Screening/Visit 1.
• 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.
• 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.
• 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).
• 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.
• 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.
• Screening systolic blood pressure >160 mm Hg or a diastolic blood pressure >90 mm Hg.
• History of anaphylaxis or cutaneous adverse drug reaction (with or without systemic symptoms) to sulfonamide antibiotics or other sulfonamide-containing drugs.
• Has a known allergy/sensitivity or contraindication to MK-7264 or its excipients (note: refer to the IB for details regarding excipients for MK-7264).
• Has donated or lost ≥1 unit of blood (approximately 300 mL) within 8 weeks prior to the first dose of MK-7264.
• 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.

Prior/Concomitant Therapy

• Requiring treatment with a therapy that does not adhere to the guidance parameters specified in Section 6.5.

Prior/Concurrent Clinical Study Experience

• Has previously received MK-7264.
• 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

Diagnostic Assessments

• Significantly abnormal laboratory tests at Screening (see Sections 8.3.6 and 8.3.7), including:
• a. alkaline phosphatase, alanine aminotransferase (ALT, SGPT), aspartate
  • aminotransferase (AST, SGOT) >200% of the upper limit of normal, or bilirubin >150% of the upper limit of normal.
  • hemoglobin <10 gm/dL, white blood cell count (WBC) <2500 mm3 (<2.5 × 103/uL), neutrophil count <1500 mm3 (<1.5 × 103/uL), platelet count <100 × 103/mm3
  • (<100 × 103/uL).
• For any of the above listed laboratory assessments, 1 repeat measurement will be allowed at the investigator’s discretion, before being considered a screen failure.

Other Exclusions

• 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.
• Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

ifestyle Considerations

Meals and Dietary Restrictions

• No restrictions are required.

Caffeine, Alcohol, and Tobacco Restrictions

• Participants who currently smoke, who have given up smoking within the past 12 months, as well as participants who are former smokers with a pack/year history greater than 20 pack-years will not be permitted in the study. For the purposes of the study, smoking is intended to include cigars, e-cigarettes, cigarettes, vapes, etc. Smoking of any kind is not permitted during the course of the study.