Computerized Cognition Testing in Participants With Mild Alzheimer's Disease (AD) Treated With Donepezil (MK-0000-318)

Study Overview
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Brief Summary
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This study aims to determine whether the Cogstate testing battery can detect improvements in cognitive function in participants with mild AD. The primary hypothesis is that for one of the Cogstate battery tests, One Card Learning (OCL), the standard deviation associated with the change from baseline in OCL measurements after 12 weeks of donepezil and placebo treatments is =<0.1

Official Title
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A Clinical Trial to Assess Cognitive Function by Repeated Computerized Testing in Patients With Mild Alzheimer's Disease Treated With Donepezil

Conditions
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Alzheimer's Disease

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets listed criteria for a diagnosis of probable AD Has a clearly documented history either in medical records or from an informant of cognitive decline over at least 6 months Has a reliable partner/caregiver who is willing to provide input by participating in assessments Has results of a physical examination and clinical laboratory tests within normal or clinically acceptable limits Can communicate with trial staff acceptably, possesses the ability to respond verbally to questions, follow instructions, complete questionnaires, and adhere to visit schedules Can read at a 9th grade level or equivalent, and has an acceptable history of academic achievement and/or employment Has a magnetic resonance imaging (MRI) scan that rules out non-AD conditions contributing to cognitive dysfunction Capably performs the CogState screening battery Has adequate visual acuity and function Females are not of childbearing potential Exclusion Criteria: Has ever received acetylcholinesterase inhibitors, memantine, or other symptomatic AD treatment including approved medical foods Has an uncontrolled, clinically significant medical condition or situation within 3 months prior to screening Has had major surgery within 3 months prior to screening Has tested positive for human immunodeficiency virus (HIV) or has evidence of an active hepatitis B infection Has a history of malignancy within the prior 5 years Is unwilling or ineligible to undergo an MRI scan Has a history of clinically important structural changes on screening MRI scan Has a clinically important history of stroke or a diagnosis of vascular dementia Has evidence of a clinically relevant non-AD neurological disorder Has a history of head trauma, or serious infectious disease affecting the brain within the prior 3-5 years Has evidence of a clinically relevant or unstable psychiatric disorder, excepting major depression in remission Has evidence of a current episode of major depression Has evidence of Type 4 or Type 5 Suicidal Ideation Has clinically significant vitamin B12 or folate deficiency in the 6 months prior to screening Is pregnant, attempting to become pregnant or is nursing children Has used any investigational drug or participated in any other clinical trial within the prior 30 days Has a history of alcoholism or drug dependency/abuse within the last 5 years Has a relative contraindication to donepezil including sick sinus syndrome, third degree heart block, active gastrointestinal (GI) bleeding, Zollinger-Ellison syndrome, uncontrolled peptic ulcer disease, or uncontrolled asthma

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo for donepezil hydrochloride capsule administered orally once a day for 16 weeks. | Drug: Placebo<br>* Placebo for donepezil hydrochloride capsule<br>|
| Experimental: Donepezil<br>During the first 4 weeks, participants received placebo for donepezil. Over the following 2 weeks, participants were treated with donepezil at 5 mg per day. Then, over the remaining 10 weeks were titrated to up to 10 mg per day donepezil based on tolerability. | Drug: Placebo<br>* Placebo for donepezil hydrochloride capsule<br>Drug: Donepezil<br>* 5 mg donepezil hydrochloride capsule.<br>* Other names: Aricept;Drug: Donepezil<br>* 10 mg donepezil hydrochloride capsule.<br>* Other names: Aricept;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. OCL is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCL questions. The score ranges from 0 to 1.5708 where a higher score means better performance. | Weeks 4, 8, 12 and 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. The percentage of correct responses to 80 OCL questions is defined as the number of correct responses x 100 divided by the number of total responses; and ranges from 0 to 100, where 100 is best, and 0 is the worst outcome. | Weeks 4, 8, 12 and 16 |