A Study to Evaluate the Effect of Gefapixant (AF-219/MK-7264) on Methacholine Hyper-reactivity in Participants With Asthma (MK-7264-009)
Condition: Asthma
MeSH terms: Asthma
Intervention: Gefapixant 50 mg; Gefapixant 300 mg; Placebo to mimic 50 mg tablets; Placebo to mimic 300 mg tablets
Intervention description: Gefapixant 50 mg tablet administered orally; Gefapixant 300 mg tablet administered orally; Sugar pill manufactured to mimic gefapixant 50 mg tablets; Sugar pill manufactured to mimic gefapixant 300 mg tablets
Intervention MeSH terms: Mitomycin; Cisplatin; Ifosfamide; Mesna
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This is a randomized, double-blind, double-dummy, placebo-controlled, three-way cross-over,
      single centre study in participants with asthma undergoing inhalation of methacholine and
      adenosine triphosphate (ATP) to assess the provocative concentration (PC20) response of two
      dose levels of gefapixant (AF-219) compared with placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women of child-bearing potential (WOCBP) (i.e., women who are not surgically sterile,
             not having had hysterectomy, bilateral tubal occlusion or bilateral oophorectomy, or
             are not postmenopausal) must have a negative pregnancy test at Screening and prior to
             randomization. WOCBP must be using 2 forms of acceptable birth control method from
             Screening through the Follow-Up Visit. Acceptable birth control methods include (of
             which 2 must be used):

               -  Established use of oral, injected or implanted hormonal methods of contraception

               -  Intrauterine device (IUD) or intrauterine system (IUS)

               -  Condom with spermicide

               -  Diaphragm with spermicide

               -  Double-barrier method (diaphragm for female participant and condom for male
                  partner with spermicidal) satisfies the requirement for 2 forms of acceptable
                  birth control. When in line with the preferred lifestyle of the participant, true
                  and complete abstinence (not periodic abstinence) is acceptable.

               -  Male participants with partners WOCBP (as defined in Inclusion No. 2) must use 2
                  methods of acceptable birth control with their partner, 1 of which must be a
                  barrier method. Contraception must start from screening and continue until 3
                  months after last dose of study drug.

          -  Non-smokers or former smokers, who stopped smoking 6 months prior to screening. Former
             smokers should not have a smoking history of more than 5 pack years (1 pack of 20
             cigarettes per day over 5 years).

          -  Physician documented history or diagnosis of asthma for at least 6 months prior to
             screening according to the Global Initiative in Asthma guidelines (GINA, 2012).

          -  Requires the use of Short acting β2-agonist therapy only (≤ 8 puffs per day) for at
             least 4 weeks prior to screening and prior to randomization.

        Exclusion Criteria:

          -  Has been hospitalized or attended the emergency department for an asthma attack in the
             12 months prior to screening.

          -  Exacerbation of asthma or lower respiratory tract infection during the 4 weeks before
             screening or prior to randomization.

          -  Upper respiratory tract infection during the 4 weeks before screening or prior to
             randomization requiring treatment with antibiotics.

          -  Inhaled or systemic corticosteroids (oral, intravenous, intramuscular) within 4 weeks
             prior to screening or prior to randomization.

          -  Short-acting or long-acting antihistamines within 48hrs or 7 days, respectively, prior
             to screening.

          -  Body mass index (BMI) <18 kg/m2 or ≥ 35 kg/m2 at screening.

          -  History of kidney/bladder stones (nephro/uro-lithiasis) within 5 years of screening.

          -  History of conditions or disorders that predispose to nephrolithiasis, such as Type 1
             renal tubular acidosis, cystinuria, gout, hyperparathyroidism, inflammatory bowel
             disease (i.e., ulcerative colitis and Crohn's disease), short bowel syndrome, or
             bariatric surgery.

          -  History of concurrent malignancy or recurrence of malignancy within 2 years prior to
             Screening (not including participants with basal cell carcinomas or cervical carcinoma
             in situ that has been successfully treated surgically).

          -  Personal or family history of congenital long QT Interval on ECG (QT) syndrome.

          -  Presence of a cardiac pacemaker.

          -  History of a diagnosis of drug or alcohol dependency or abuse within approximately the
             last 3 years.

          -  Diagnosis of depression, psychosis, bipolar disorder, or schizoaffective disorder.

          -  Participants with diabetes Type I or uncontrolled diabetes Type II or Glycosylated
             Hemoglobin (HbA1c) > 8.0% at screening.

          -  Any condition possibly affecting drug absorption e.g., gastrectomy, gastroplasty, any
             type of bariatric surgery, vagotomy, or bowel resection.

          -  History of cutaneous adverse drug reaction to sulphonamides or signs or symptoms
             suggestive of anaphylaxis to sulphonamides.

          -  Requiring concomitant therapy with prohibited medications at screening or prior to
             randomization.

          -  Pregnant or breastfeeding woman.

          -  Donation of sperm from Screening until 3 months after the last dose of study drug.

          -  Male participants with pregnant female partners.

          -  Treatment with an investigational drug within 30 days or five half-lives preceding the
             first dose of study medication or plans to take another investigational drug within 30
             days of study completion.

          -  Donation or loss of 400 mL or more of blood or donations of plasma within eight (8)
             weeks prior to initial dosing or longer if required by local regulation.