| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Acute cough in participants with induced viral upper respiratory tract infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Acute cough in participants with induced viral upper respiratory tract infection |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10047482 |
| E.1.2 | Term | Viral upper respiratory tract infection |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of MK-7264 on cough frequency as measured while awake during a 24-hour period |
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of MK-7264 on the perception of cough severity
2. To evaluate the efficacy of MK-7264 on cough-specific quality of life
3. To evaluate the safety and tolerability of MK-7264 |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| Future Biomedical Research. Merck will conduct Future Biomedical Research on DNA collected during this clinical trial. 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. |
|
| E.3 | Principal inclusion criteria |
Participants are eligible to be included in the study only if all of the following criteria apply:
1. In good general health with no clinically relevant abnormalities based on the medical history, physical examination, vital sign measurements, clinical laboratory evaluations (ie, hematology, clinical chemistry, and urinalysis), and 12-lead ECG.
2. Susceptible to HRV-16, as evidenced by a serum-neutralizing antibody titer of 1:4 or less, or the definition used by the individual clinic.
3. Between 18 and 55 years of age (inclusive) at the Screening Visit, of either gender, and of any race.
4. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP)
OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 14 days after the last dose of study treatment.
5. 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 study without participating in Future Biomedical Research.
6. Demonstrates an ability to follow study procedures (including use of the digital cough recording device [VitaloJAK™] and completing the PROs [Cough Severity VAS, CSD, LCQ-acute, and WURSS-24]) to the satisfaction of the investigator/qualified designee prior to randomization.
7. Has clinical laboratory tests (complete blood count [CBC], blood chemistries, including urine pregnancy for female participants of childbearing potential [ie, who have started menstruating], and urinalysis) conducted during Screening documented to be clinically acceptable to the investigator before beginning the Treatment Period. A female participant of childbearing potential (ie, who has started menstruating) must have a negative urine pregnancy test (or a negative serum pregnancy test, if required) at both the Screening Visit and Baseline Visit (Day -1) to be considered eligible for the trial. |
|
| E.4 | Principal exclusion criteria |
Participants are excluded from the study if any of the following criteria apply:
1. Donated blood within 56 days or donated plasma within 7 days prior to dosing.
2. Has forced expiratory volume in one second (FEV1) <70% of predicted and/or FEV1/forced vital capacity (FVC) ratio <80%.
3. Has a history of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability ( ie, systemic allergic reaction) to prescription or nonprescription drugs or food.
4. Has recent history of an upper or lower respiratory tract infection or recent significant change in pulmonary status within 4 weeks of the Baseline Visit (Day -1).
5. Has estimated glomerular filtration rate (eGFR) <50 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) formula at Screening.
6. Has a history of cancer (malignancy).
7. Has any condition possibly affecting drug absorption (eg, gastrectomy, gastroplasty, any type of bariatric surgery, or vagotomy).
8. Has screening systolic blood pressure (SBP) >160 mm Hg or a diastolic blood pressure >90 mm Hg.
9. Has a body mass index <18 kg/m2 or ≥40 kg/m2.
10. Had major surgery or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to Screening.
11. Has history of a cutaneous adverse drug reaction to sulfonamides or signs and symptoms suggestive of anaphylaxis to sulfonamides.
12. Has a history of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases that might expose the participant to risk by participating in the trial or investigational product administration or confound the results of the trial, or interfere with the participant’s participation for the full duration of the trial, and, in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this trial.
13. Is mentally or legally incapacitated, has significant emotional problems at the time of Screening, or is expected to during the conduct of the trial, or has a history of a clinically significant psychiatric disorder in the last 5 years. Participants who have had situational depression may be enrolled in the trial at the discretion of the investigator.
14. A WOCBP who has a positive urine pregnancy test within 72 hours before the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
15. Has received medications to treat an acute viral URTI within 24 hours of study enrollment (defined as Day -1) (including dextromethorphan, diphenhydramine, and narcotic analgesics).
16. Has received medications within 14 days prior to randomization or needs to continue to receive any treatment (prescription or OTC) during the current trial, including antacids, high-dose multivitamins, nutritional supplements, and herbal preparations, beginning approximately 2 weeks (or 5 half-lives of the prior/concomitant medication) prior to administration of the initial dose of study treatment, throughout the trial, until the post-treatment visit (Day 8).
17. Has previously received MK-7264.
18. Has participated in another investigational trial within 4 weeks (or 5 half-lives of the investigational product used in the other trial), whichever is greater, prior to the screening visit (the window will be derived from the date of the last visit in the previous trial) OR plans to take another investigational drug or biologic within 30 days of study completion of this current trial.
19. Has significantly abnormal laboratory tests at Screening, including:
a) Alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), or bilirubin >150% of the upper limit of normal (ULN);
b) Hemoglobin <10 gm/dL, red blood cell (RBC) count < lower limit of normal (LLN) range, neutrophil count <LLN, platelet count <100 × 103/mm3
20. Has a clinically significant finding in a 12-lead ECG.
21. Current smoker, smoker within 5 years of Screening, or former smoker with a smoking history >20 pack-years.
22. Consumes >3 glasses of alcoholic beverages per day. Participant that consumes 4 glasses of alcoholic beverages per day may be enrolled at the discretion of the investigator.
23. Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day.
24. Is a regular user of cannabis or any illicit drugs, or has a history of drug (including alcohol) abuse within approximately 3 years of Screening. Participant must have a negative urine drug screen prior to randomization.
25. Is or has an immediate family member who is investigational site or sponsor staff directly involved with this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Awake coughs per hour on Day 3 of treatment. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Cough Severity VAS score measured as change from baseline on Day 3.
CSD score measured as change from baseline on Day 3
LCQ-acute score measured as change from baseline on Day 3
Number of participants experiencing AEs.
Number of participants discontinuing study treatment due to AEs |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Day 3 (for efficacy) and throughout trial (for safety) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The overall study ends when the last participant completes the last study-related phone-call or visit, withdraws from the study or is lost to follow-up (ie, the participant is unable to be contacted by the investigator). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | 7 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 10 |
| E.8.9.2 | In all countries concerned by the trial days | 2 |
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