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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Asthma
• Intervention / Treatment: Drug: Low-Dose MK-8351; Drug: High-Dose MK-8351; Drug: Placebo to MK-8351

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.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Anticipated): April 1, 2014
• Study Completion (Anticipated): April 1, 2014

Study Registration Dates

• First Submitted: August 16, 2013
• First Submitted That Met QC Criteria: August 16, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Estimate): July 16, 2015
• Last Update Submitted That Met QC Criteria: July 15, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Other Study ID Numbers: 8351-003; MK-8351-003 (Other Identifier: Merck Study Number)