A Single-Dose Study of MK-8351 in a Lung Allergen Challenge (MK-8351-003)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Low-Dose MK-8351
* Drug: High-Dose MK-8351
* Drug: Placebo to MK-8351


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose MK-8351<br>Low-dose MK-8351 administered as single inhaled dose. | Drug: Low-Dose MK-8351<br>* Single administration of low-dose MK-8351.<br>|
| Experimental: High-Dose MK-8351<br>High-dose MK-8351 administered as a single inhaled dose. | Drug: High-Dose MK-8351<br>* High-Dose MK-8351 administered as a single inhaled dose.<br>|
| Placebo Comparator: Placebo to MK-8351<br>Matching placebo to low-dose or high-dose MK-8351 administered as a single inhaled dose. | Drug: Placebo to MK-8351<br>* Single-Dose Matching placebo to high-dose or low-dose MK-8351.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-3hr of FEV1 Percent Change From Baseline |  | 3 Hours | 
| Number of Participants Experiencing Adverse Events (AEs) |  | Up to 14 Days | 
| Number of Participants Discontinuing Study Treatment Due to AEs |  | Up to 72 Hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24h of MK-8351 |  | Up to 24 Hours Post-Dose | 
| AUC0-last of MK-8351 |  | Up to 72 Hours Post-Dose | 
| AUC0-∞ of MK-8351 |  | Up to 72 Hours Post-Dose | 
| Maximum Plasma Concentration (Cmax) of MK-8351 |  | Up to 72 Hours Post-Dose | 
| Time to Maximum Plasma Concentration (Tmax) of MK-8351 |  | Up to 72 Hours Post-Dose | 
| Apparent Half-Life (t1/2) of MK-8351 |  | Up to 72 Hours Post-Dose |