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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Dementia

Intervention / Treatment
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* Drug: MK3134
* Drug: Comparator: Placebo
* Drug: Donepezil
* Drug: MK3134


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 |