a study to evaluate the effect of gefapixant (af-219/mk-7264) on methacholine hyper-reactivity in participants with asthma (mk-7264-009)

Conditions: Asthma

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.