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

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: Placebo
Drug: Donepezil

Registration Number: NCT02064920

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 36

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo for donepezil hydrochloride capsule administered orally once a day for 16 weeks.
Donepezil	Placebo	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.
Donepezil	Donepezil	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.

Primary Outcome Measures

Name	Time	Method
One-card Learning (OCL) Measurement Over 12 Weeks of Treatment	Weeks 4, 8, 12 and 16	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment	Weeks 4, 8, 12 and 16	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.