Cognition Platform Study in Participants at Risk for Alzheimer's Disease (AD) (MK-0000-413)

Study Overview
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Brief Summary
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The main purpose of this study is to assess the ability of a repeated high-frequency site-based computerized cognitive assessment to evaluate the potential treatment effects of donepezil (MK-0000) compared with placebo among participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD). The primary study hypothesis is that the average percentage of correct responses on one card learning (OCL) task will be ≥2 percentage points in participants receiving donepezil compared with participants receiving placebo.

Official Title
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A Clinical Study to Evaluate a Cognitive Platform to Support Development of Symptomatic Therapies in Participants at Risk for Alzheimer's Disease

Conditions
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Alzheimer's Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: Donepezil
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has an Mini Mental State Examination (MMSE) score between 18 and 28 (inclusive) at Screening (Visit 1) and Baseline (Visit 2) Has a diagnosis of mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) Has an Modified Hachinski Ischemia Scale (MHIS) score of ≤4 Must have a reliable and competent study partner/informant who accompanies participant to study visits and participates in assessments Be willing to provide a blood sample for Apolipoprotein E (APOE) genotyping Does not have intellectual disability Be able to speak, read, hear, and understand the language of the study staff and the Informed Consent Form (ICF) Be able and willing to adhere to the study visit schedule Have visual acuity, visual function, hearing, and gross and fine motor skills adequate to support study participation Be capable of performing the Cogstate battery assessments, as demonstrated at the Baseline/Familiarization Visit (Visit 2) A female participant is eligible to participate if she is a woman of nonchildbearing potential (WONCBP) Exclusion Criteria: Is at imminent risk of self-harm Has evidence of a clinically relevant neurological disorder other than AD at screening, including but not limited to: Parkinson's disease, frontotemporal dementia, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, progressive supranuclear palsy, dementia with Lewy bodies, other types of dementia, neurosyphilis or that led to persistent cognitive deficits, or has a history of seizures or epilepsy within the last 5 years before screening Has a known history of stroke or has a diagnosis of vascular dementia Has history of multiple episodes of head trauma, or head trauma resulting in protracted loss of consciousness, or serious infectious disease affecting the brain, within the prior 3-5 years Has evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), including schizophrenia or other psychotic disorder, bipolar disorder, major depression, or delirium Has a recent or ongoing, uncontrolled, clinically significant medical condition within 2 months of the Screening visit Has a history of cancer Has a relative contraindication to donepezil including sick sinus syndrome, first, second, or third-degree heart block, bradycardia, active gastrointestinal (GI) bleeding, Zollinger-Ellison syndrome, uncontrolled peptic ulcer disease, or uncontrolled asthma Has a history of significant multiple and/or severe allergies or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food. Exception: Participants with selected allergies may be enrolled with Sponsor's approval Is positive for Hepatitis B surface antigen (HBsAg), hepatitis C antibodies or human immunodeficiency virus (HIV) [participants with a history of chronic hepatitis C virus with a documented cure and/or a positive serologic test for HCV with a negative HCV viral load may be included] Has clinically significant vitamin B12 or folate deficiency in the 6 months immediately before screening, or vitamin B12 or folate deficiency in addition to increased serum homocysteine and methylmalonic acid levels at screening Has prior AD treatment Has participated in another investigational study within 4 weeks Has a known history of structural changes on screening magnetic resonance imaging (MRI) scan that are clinically important, including signs indicative of vascular dementia, large infarct, lacunes in critical areas, space-occupying lesions, or extensive white matter disease Is unwilling to or not eligible to undergo a MRI scan (if a prior MRI scan is not available) Is pregnant, is attempting to become pregnant, or is nursing children Has a history of alcoholism or drug dependency/abuse within the last 5 years prior to the Screening visit Consumes greater than 3 glasses of alcoholic beverages per day Consumes excessive amounts, defined as greater than 6 servings of coffee, tea, cola, energy drinks, or other caffeinated beverages per day Is a regular user of cannabis, any illicit drugs or has a history of drug abuse within approximately 5 years. A participant who is a recreational user of cannabis or other drugs within the past 2 years can be enrolled as long as recreational use does not meet the definition of drug abuse and participant agrees to refrain from substance use for duration of study participation Participants must have a negative urine drug screen (UDS) prior to randomization Had major surgery within 3 months prior to the Screening visit that would interfere in the participant's ability to fully participate in the study Has undergone neuropsychological testing (including the MMSE) or cognitive remediation in the past 4 weeks Is or has an immediate family member who is investigational site or Sponsor staff directly involved with this study

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donepezil<br>Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days. | Drug: Donepezil<br>* Donepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56.<br>* Other names: Aricept;|
| Placebo Comparator: Placebo<br>Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days. | Drug: Placebo<br>* Dose matched placebo capsule QD, orally for Days 1-56.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Correct Responses on the One Card Learning (OCL) Task to Week 8 | OCL uses a pattern separation paradigm to assess visual memory. Tthe percentage change from baseline in correct responses on the OCL task up to Week 8 will be compared in participants receiving donepezil with participants receiving placebo. | Baseline, Up to Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in the Overall Standard Deviation (sd) in Average OCL Task (Arcsine Square Root Transformed) to Week 8 | OCL uses a pattern separation paradigm to assess visual memory. The percentage change from baseline in correct responses on the OCL task up to Week 8 will be compared in participants receiving donepezil with participants receiving placebo. | Baseline, Up to Week 8 | 
| Percentage of Correct Responses on the OCL Task | OCL uses a pattern separation paradigm to assess visual memory. The percentage of correct responses on the OCL task will be compared in participants receiving donepezil with participants receiving placebo up to approximately Week 8. | Up to approximately Week 8 |