A Study to Evaluate the Effects of MK-0249 and an Alzheimer's Disease Medication on Cognitive Function in Adults With Alzheimer's Disease (MK-0249-023)

Study Overview
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Brief Summary
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This study will evaluate acute symptomatic improvements in cognitive performance in healthy elderly participants with mild-to-moderate Alzheimer's disease. A four-week pilot study will first evaluate the CogState computerized cognitive battery in participants who are not receiving treatment. After completion of the pilot study, participants will be randomized to receive Placebo, Donepezil 5 mg, MK-0249 7.5 mg, and MK-0249 25 mg. After each drug administration the participants will be given the CogState computerized cognitive battery to assess cognitive performance. The primary hypotheses are that cognitive performance in participants with Alzheimer's disease, or in healthy participants, is improved by the administration of a single oral 5 mg dose of Donepezil as compared to placebo.

Official Title
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A Randomized Clinical Trial To Evaluate the Single Dose Acute Effects of MK-0249 and Donepezil On Cognitive Function In Adult Patients With Alzheimer's Disease

Conditions
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Alzheimer's Disease, Dementia

Intervention / Treatment
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* Drug: MK-0249 7.5 mg
* Drug: MK-0249 25 mg
* Drug: Donepezil 5mg
* Drug: Placebo to MK-0249
* Drug: Placebo to Donepezil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient Specific: Female is not of reproductive potential Male who has a female partner(s) of child bearing potential, agrees to use acceptable method of contraception during the study Has at least 10 years of education or work history Has been a nonsmoker or has not used nicotine for at least 6 months Has a diagnosis of mild-to-moderate Alzheimer's Disease Has a reliable caregiver who consents to accompany the patient to all clinic visits, provide information to the study staff, and return for follow-up visits and procedures Healthy Elderly Volunteer Specific: Is in good general health Has no clinically significant abnormality on electrocardiogram (ECG) Exclusion Criteria: Participant Specific: Has a history of a neurological disorder other than Alzheimer's disease Is living in a nursing home Has a history of stroke Has a history of psychotic disorder, an active major depressive disorder, or history of schizophrenia Has a history of a sleep disorder Has a history of a cardiovascular disorder Has a history of malignancy Is participating or has participated in a study with an investigational compound, device, or vaccine for Alzheimer's disease Consumes greater than 6 servings of caffeine (coffee, tea or cola etc.) per day Consumes greater than 3 alcoholic beverages per day Has had major surgery, donated or loss blood in past 8 weeks Healthy Elderly Volunteer Specific: Is mentally or legally incapacitated, has significant emotional problems, or has a history of a psychiatric disorder over the last 5-10 years

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PBO→MK-7.5→DON→MK-25<br>Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-7.5→PBO→MK-25→DON<br>Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: DON→MK-25→PBO→MK-7.5<br>Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-25→DON→MK-7.5→PBO<br>Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: PBO→MK-25→MK-7.5→DON<br>Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-7.5→DON→PBO→MK-25<br>Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: DON→MK-7.5→MK-25→PBO<br>Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-25→PBO→DON→MK-7.5<br>Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: PBO→DON→MK-25→MK-7.5<br>Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-7.5→MK-25→DON→PBO<br>Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: DON→PBO→MK-7.5→MK-25<br>Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|
| Experimental: MK-25→MK-7.5→PBO→DON<br>Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period. | Drug: MK-0249 7.5 mg<br>* 4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period<br>Drug: MK-0249 25 mg<br>* 5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period<br>Drug: Donepezil 5mg<br>* One 5 mg tablet, single oral dose during each crossover period<br>* Other names: Aricept;Drug: Placebo to MK-0249<br>* Five tablets, single oral dose during each crossover period<br>Drug: Placebo to Donepezil<br>* One over-encapsulated capsule, single oral dose during each crossover period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Participants With Alzheimer's Disease | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. | Baseline and 5-7 hours post-dose | 
| Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Healthy Participants | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. | Baseline and 5-7 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Participants With Alzheimer's Disease. | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. | Baseline and 5-7 hours post-dose | 
| Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Healthy Participants. | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. | Baseline and 5-7 hours post-dose |