Clinical trial NCT01926002: A Single-Dose Study of MK-8351 in a Lung Allergen Challenge (MK-8351-003)
Official title: A Multicenter Randomized Clinical Trial to Study the Effects of Single Doses of MK-8351 on the Early Asthmatic Response to a Lung Allergen Challenge
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Asthma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2013-08-20
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary hypothesis of the study is single doses of MK-8351 will reduce the baseline early asthmatic response (EAR) as assessed by area under the curve from 0-3 hours (AUC0-3hr) of forced expiratory volume (FEV1) when compared to placebo.

Detailed description: This is a randomized, placebo-controlled, 4-period study. Eligible patients will undergo a single-blind phase in Period 1, followed by 3 periods during which they will receive low-dose MK-8351, high-dose MK-8351, or matching placebo as a single dose in a random sequence crossover study design.

Eligibility criteria: Inclusion Criteria:

* Females of non-childbearing potential (at least 1 year post-menopausal, post-hysterectomy, post-oophorectomy, or with tubal ligation);
* Males with a female partner of childbearing potential must agree to use a medically acceptable method of contraception during and up to 120 days after the last dose of study medication;
* Body Mass Index (BMI) \>=17 kg/m\^2 and \<=33 kg/m\^2
* Non-smoker and non-user of nicotine or nicotine-containing products for at least 6 months prior to enrollment;
* History of allergen-induced asthma for at least 6 months prior to enrollment;
* Able to perform reproducible pulmonary function testing;
* Positive methacholine challenge test prior to receiving study medication;
* Allergic response to house dust mite allergen or standardized cat pelt or hair allergen extract;
* Ability to tolerate sputum induction and to produce adequate sputum.

Exclusion Criteria:

* History of clinically significant disease or disorder;
* History of malignancy;
* History of significant multiple and/or severe allergies;
* History of milk or lactose allergies or intolerance;
* History of anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food;
* Positive for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies;
* History of major surgery within 3 months prior to enrollment;
* Participation in another investigational trial within 4 weeks of screening;
* Lactating females;
* Inability to refrain from, or anticipates the use of, any medication including herbal remedies during the trial period;
* History of receiving anti-immunoglobulin E (IgE) or immunotherapy;
* History of serious allergies to drug or a history of hypersensitivity to inhaled salbutamol, antihistamines, or any other potential asthma/anaphylaxis rescue medication;
* History of hospitalization for asthma-related illness within 3 months of screening;
* History of emergent care more than twice in the last 12 months for asthma-related illness;
* History of life-threatening asthma;
* Consumes \>4 glasses of alcoholic beverage per day;
* Consumes \>6 servings of coffee, tea, cola, energy drinks or other caffeinated beverages per day;
* History or or current use of illicit drugs within past 24 months.

Primary outcomes:
measure: AUC0-3hr of FEV1 Percent Change From Baseline
timeFrame: 3 Hours
measure: Number of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 14 Days
measure: Number of Participants Discontinuing Study Treatment Due to AEs
timeFrame: Up to 72 Hours
Secondary outcomes:
measure: AUC0-24h of MK-8351
timeFrame: Up to 24 Hours Post-Dose
measure: AUC0-last of MK-8351
timeFrame: Up to 72 Hours Post-Dose
measure: AUC0-∞ of MK-8351
timeFrame: Up to 72 Hours Post-Dose
measure: Maximum Plasma Concentration (Cmax) of MK-8351
timeFrame: Up to 72 Hours Post-Dose
measure: Time to Maximum Plasma Concentration (Tmax) of MK-8351
timeFrame: Up to 72 Hours Post-Dose
measure: Apparent Half-Life (t1/2) of MK-8351
timeFrame: Up to 72 Hours Post-Dose
Other outcomes:
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