MK-7264 Phase 3 study in adult participants with chronic cough (PN030)

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2017-003559-49-DE
• Date of registration: 22/01/2018
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: MK-7264 Phase 3 study in adult participants with chronic cough (PN030)
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 12-Month Study to Evaluate the Efficacy and Safety of MK-7264 in Adult Participants with Chronic Cough (PN030)
• Date of first enrolment: 09/03/2018
• Target sample size: 1290
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-003559-49
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Off-treatment Durability Study Period is observational If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Canada, China, Colombia, Czech Republic, Denmark, Germany, Guatemala, Hungary, Italy, Malaysia, New Zealand, Peru, Poland, South Africa, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: GCTO
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: GCTO
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

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 informed consent.
5. A female participant is eligible to participate if she is not pregnant Contraceptive Guidance and Pregnancy Testing), 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 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.


Off-treatment Durability Study Period:
1. Participant completed the Main and Extension Study Periods, on study intervention, through the evening prior to Visit 13.
2. Participant completed the baseline, (Visit 2, Day 0) ePRO diaries (ie, LCQ and EQ5D-5L).
3. Participant completed the Visit 13 LCQ.
4. Participant was at least 80% compliant with completion of the Cough Severity VAS throughout all study periods.
5. Participant was at least 80% compliant with taking the study intervention throughout the Main and Extension Study Periods.
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 860
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 430

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.

Off-treatment Durability Study Period:
1. Participant is expected to need to take an angiotensin converting enzyme inhibitor during the Off-treatment Durability

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

chronic cough
MedDRA version: 21.1 Level: LLT Classification code 10066656 Term: Chronic cough System Organ Class: 100000004855

Intervention(s)

Product Code: MK-7264
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: gefapixant
CAS Number: 1015787-98-0
Current Sponsor code: MK-7264
Other descriptive name: AF-219
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 45-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Code: MK-7264
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: gefapixant
CAS Number: 1015787-98-0
Current Sponsor code: MK-7264
Other descriptive name: AF-219
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): - 24-hour coughs per hour at Week 24
- Number of participants experiencing an adverse event (AE)
- Number of participants discontinuing study intervention due to an AE

Timepoint(s) of evaluation of this end point: Week 24 (Efficacy) Throughout study (Safety)

Secondary Objective: 1. To evaluate the efficacy of MK-7264 in reducing cough frequency as measured while awake during a 24-hour period
2. To evaluate the ability of MK-7264 to provide a clinically significant improvement in cough specific quality of life
3. 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
4. To evaluate the efficacy of MK-7264 in improving self-rated cough severity

Main Objective: 1. To evaluate the efficacy of MK-7264 in reducing cough frequency as measured over a 24-hour period
2. To evaluate the safety and tolerability of MK-7264

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 24

Secondary end point(s): - Awake coughs per hour at Week 24
- Proportion of participants with a =1.3 point increase from baseline in LCQ total score at Week 24
- Proportion of participants with a =30% reduction from baseline in 24-hour coughs per hour at Week 24
- Proportion of participants with a =1.3 point reduction from baseline in mean weekly Cough Severity Diary (CSD) total score at Week 24
- Proportion of participants with a =2.7 point reduction from baseline in mean weekly CSD total score at Week 24
- Proportion of participants with =30 mm reduction from baseline in Cough Severity Visual Analog Scale (VAS) score at Week 24

Secondary ID(s)

123007

2017-003559-49-CZ

7264-030

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 09/03/2018
Contact: