Asthma
Conditions
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.
Interventions
DRUGLow-Dose MK-8351
Single administration of low-dose MK-8351.
DRUGHigh-Dose MK-8351
High-Dose MK-8351 administered as a single inhaled dose.
DRUGPlacebo to MK-8351
Single-Dose Matching placebo to high-dose or low-dose MK-8351.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Maximum Plasma Concentration (Cmax) of MK-8351 | Up to 72 Hours Post-Dose |
| AUC0-24h of MK-8351 | Up to 24 Hours Post-Dose |
| Apparent Half-Life (t1/2) of MK-8351 | Up to 72 Hours Post-Dose |
| Time to Maximum Plasma Concentration (Tmax) of MK-8351 | Up to 72 Hours Post-Dose |
| AUC0-last of MK-8351 | Up to 72 Hours Post-Dose |
| AUC0-∞ of MK-8351 | Up to 72 Hours Post-Dose |
Outcome results
None listed