BOLD Functional Magnetic Resonance Imaging (fMRI) and Cerebral Blood Flow Measurements as Biomarkers for Cognition Enhancing Drugs (3134-006)

A 4-Period, Placebo-Controlled, Crossover Study to Evaluate the Utility and Feasibility of BOLD fMRI and Cerebral Blood Flow Measurements as Biomarkers for Cognition Enhancing Drugs (Donepezil and MK3134)

This study will evaluate functional magnetic resonance imaging (fMRI) and methods for measuring drug induced changes in cerebral blood flow as biomarkers for attention-improving drugs.

Study Overview

• Status: Completed
• Conditions: Dementia
• Intervention / Treatment: Drug: MK3134; Drug: Comparator: Placebo; Drug: Donepezil; Drug: MK3134

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Subject is a nonsmoker
• Subject is in generally good health
• Subject has normal (or corrected to normal) vision and hearing
• Subject is right-handed

Exclusion Criteria:

• Subject has a history of any illness that would make participation unsafe or would make the study results difficult to interpret
• Subject has a history of stroke, seizures, or major neurological disorders
• Subject has a history of cancer
• Subject has permanent cosmetic or metallic implants that would interfere with measurements
• Subject has a history of sleep apnea
• Subject has a history of head injury/trauma

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I; Subjects will receive placebo, MK3134, and donepezil in one of four treatment sequences.	Drug: MK3134; Single dose 25 mg (5 x 5 mg) MK3134 capsules in one of the four treatment periods.; Drug: Comparator: Placebo; Placebo capsules only in one of the four treatment periods.; Drug: Donepezil; Single dose 5 mg donepezil capsules in two of the four treatment periods.; Other Names: Aricept; Drug: MK3134; Single doses of 1 mg, 5 mg, or 25 mg MK3134 capsules in the assigned treatment periods
Experimental: Part II; Subjects will receive placebo and three different doses of MK3134 (1 mg, 5 mg, and 25 mg) in one of four treatment sequences.	Drug: MK3134; Single dose 25 mg (5 x 5 mg) MK3134 capsules in one of the four treatment periods.; Drug: Comparator: Placebo; Placebo capsules only in one of the four treatment periods.; Drug: MK3134; Single doses of 1 mg, 5 mg, or 25 mg MK3134 capsules in the assigned treatment periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part I: Difference in number of voxels showing a positive response after treatment with donepezil and placebo	3.5 to 4.5 hours after study drug administration
Part I: Difference in number of voxels activated for both faces and scenes after treatment with donepezil and placebo	3.5 to 4.5 hours after study drug administration
Part II: Number of voxels showing a positive response after varying doses of MK3134 compared to placebo	3.5 to 4.5 hours after study drug administration
Part II: Number of voxels activated for both faces and scenes after varying doses of MK3134 compared to placebo	3.5 to 4.5 hours after study drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Part I: Difference in arterial transit time as measured by arterial spin labeling after treatment with donepezil and placebo	3.5 to 4.5 hours after study drug administration
Part I: Difference in Pulsatility index after treatment with donepezil and placebo	5 hours after study drug administration
Part I: Test-retest reproducibility of the BOLD fMRI and cerebral blood flow measurements in donepezil treated subjects	1 to 5 weeks
Part II: Change in arterial transit time after treatment with placebo and varying doses of MK3134	3.5 to 4.5 hours after study drug administration
Part II: Change in Pulsatility index after treatment with placebo and varying doses of MK3134	5 hours after study drug administration

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: April 23, 2009
• First Submitted That Met QC Criteria: April 23, 2009
• First Posted (Estimate): April 24, 2009

Study Record Updates

• Last Update Posted (Estimate): July 30, 2015
• Last Update Submitted That Met QC Criteria: July 29, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Dementia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 3134-006; 2009_583