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

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

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.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Alzheimer's Disease
• Intervention / Treatment: Drug: Donepezil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital-CALHN Memory Trials ( Site 0031)
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health ( Site 0030)
• United States
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network ( Site 0010)
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0013)
    • Lady Lake, Florida, United States, 32159
      • Charter Research - Lady Lake ( Site 0025)
  • Georgia
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta ( Site 0005)
    • Savannah, Georgia, United States, 31405
      • iResearch Savannah ( Site 0023)
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Pennington Biomedical Research Center ( Site 0006)
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Insight Clinical Trials ( Site 0020)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials - Fort Worth - West Rosedale ( Site 0022)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Donepezil; 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; Donepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56.; Other Names: Aricept; Donepezil hydrochloride; MK-0000
Placebo Comparator: Placebo; Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.	Drug: Placebo; Dose matched placebo capsule QD, orally for Days 1-56.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8	One Card Learning (OCL) uses a pattern separation paradigm to assess visual memory. The change from baseline of correct responses on the OCL task up to Week 8 is compared in participants receiving donepezil with participants receiving placebo. Change from baseline was the averaged correct response rate at Week 8 minus the correct response rate at baseline.	Baseline, Up to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8	OCL uses a pattern separation paradigm to assess visual memory. Change in standard deviation from baseline for correct response rate on the OCL task up to Week 8 is compared in participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) receiving donepezil with participants receiving placebo. Change from baseline was the standard deviation for correct response rate at Week 8 minus the standard deviation for correct response rate at baseline. Standard deviations are reported in arcsine square root (sqrt) transformed correct response (CR) rate.	Baseline, Up to Week 8
Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil	OCL uses a pattern separation paradigm to assess visual memory. The change from baseline of correct responses on the OCL task up to Week 8 in participants receiving donepezil is presented. Change from baseline was the averaged correct response rate at Week 8 minus the correct response rate at baseline. Per protocol, the placebo group was not included in this analysis.	Baseline, Up to Week 8

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): January 20, 2023
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: January 26, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 29, 2021

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: July 24, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neurotransmitter Agents; Cholinergic Agents; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: 0000-413; MK-0000-413 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No