A Dose Escalation Study of Gefapixant (AF-219/MK-7264) in Refractory Chronic Cough (MK-7264-010)
Condition: Refractory Chronic Cough
MeSH terms: Cough
Intervention: Gefapixant; Placebo (for gefapixant)
Intervention description: Gefapixant 7.5 and 50mg tablets administered orally; Placebo to gefapixant 7.5 and 50mg tablets administered orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      A randomized, double-blind, placebo-controlled, crossover, dose escalation study to assess
      the efficacy and tolerability of gefapixant (AF-219; MK-7264) in participants with refractory
      chronic cough.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Chest radiograph or computed tomography (CT) thorax within the last 12 months not
             demonstrating any abnormality considered to be significantly contributing to the
             chronic cough

          -  Refractory chronic cough for at least one year: a cough that is unresponsive to at
             least 8 weeks of targeted treatment for identified underlying triggers including
             reflux disease, asthma and post-nasal drip or unexplained cough: a cough for which no
             objective evidence of an underlying trigger can be determined after investigation

          -  Score of ≥ 40 mm on the Cough Severity Visual Analog Scale (VAS) at Screening

          -  Women of child-bearing potential must use 2 forms of acceptable birth control method
             from Screening through the Follow-Up Visit.

          -  Male participants and their partners of child-bearing potential must use 2 methods of
             acceptable birth control from Screening until 3 months after the last dose of study
             drug.

          -  Written informed consent.

          -  Willing and able to comply with all aspects of the protocol.

        Exclusion Criteria:

          -  Current smoker

          -  Individuals who have given up smoking within the past 6 months, or those with >20
             pack-year smoking history

          -  Treatment with an angiotensin converting enzyme (ACE)-inhibitor as the potential cause
             of a participant's cough, or requiring treatment with an ACE-inhibitor during the
             study or within 4 weeks prior to the Baseline Visit (Day 0)

          -  Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) < 60%

          -  History of upper respiratory tract infection or recent significant change in pulmonary
             status within 4 weeks of the Baseline Visit (Day 0)

          -  History of opioid use within 1 week of the Baseline Visit (Day 0)

          -  Requiring concomitant therapy with prohibited medications

          -  Body mass index (BMI) <18 kg/m^2 or ≥ 37 kg/m^2

          -  History of concurrent malignancy or recurrence of malignancy within 2 years prior to
             Screening (not including participants with <3 excised basal cell carcinomas)

          -  History of a diagnosis of drug or alcohol dependency or abuse within approximately the
             last 3 years

          -  Any condition possibly affecting drug absorption (e.g., gastrectomy, gastroplasty, any
             type of bariatric surgery, vagotomy, or bowel resection)

          -  Screening systolic blood pressure (SBP) >160 mmHg or a diastolic blood pressure (DBP)
             >90 mmHg

          -  Clinically significant abnormal electrocardiogram (ECG) at Screening

          -  Personal or family history of congenital long QT syndrome or family history of sudden
             death

          -  Cardiac pacemaker

          -  Significantly abnormal laboratory tests at Screening

          -  Breastfeeding

          -  Treatment with an investigational drug (except gefapixant) or biologic within 60 days
             preceding the first dose of study medication or plans to take another investigational
             drug or biologic within 30 days of study completion

          -  Blood donation within 56 days or plasma donation within 7 days prior to dosing

          -  Other severe, acute, or chronic medical or psychiatric condition or laboratory
             abnormality that may increase the risk associated with trial participation or
             investigational product administration or may interfere with the interpretation of
             trial results