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CompletedNCT04730635Updated Oct 28, 2024Results posted

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

A Phase 1 interventional study of Donepezil and Placebo in Alzheimer's Disease and Mild Cognitive Impairment, sponsored by Merck Sharp & Dohme LLC. Completed at 10 sites in 2 countries. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-10-28.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
44
Allocation
Randomized
Ages
55 Years to 85 Years
Sex
All
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Study summary

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.

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Conditions studied

  • Alzheimer's Disease
  • Mild Cognitive Impairment
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In context

Alzheimer Disease

3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.

This study's enrollment of 44 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
55 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
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Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
44 participants (actual)

Study arms

  • 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

  • Placebo comparator
    Placebo

    Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.

    Drug: Placebo

Interventions

  • DrugDonepezil

    Donepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56.

    Also known as: MK-0000, Donepezil hydrochloride, Aricept

  • DrugPlacebo

    Dose matched placebo capsule QD, orally for Days 1-56.

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What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline, Up to Week 8

Secondary outcomes

  1. 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.

    Time frame: Baseline, Up to Week 8

  2. 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.

    Time frame: Baseline, Up to Week 8

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Results

Posted Oct 28, 2024

Participant flow

Treatment-naïve male and female participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) between the ages of 55 and 85 years (inclusive) will be enrolled in this trial.

Participant flow — Overall Study
MilestoneDonepezilPlacebo
Started2915
Completed2814
Not completed11
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject01

Outcome measures

PrimaryChange 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.

Time frame:
Baseline, Up to Week 8
Reported as:
Mean · Proportion of correct response
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8
Proportion of correct responseDonepezilPlacebo
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 80.055 ± 0.0780.034 ± 0.091
Statistical analysis
  • Donepezil vs Placebo · Posterior probability: 46.30
SecondaryChange 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.

Time frame:
Baseline, Up to Week 8
Reported as:
Number · Arcsine sqrt transformed proportion CR
Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8
Arcsine sqrt transformed proportion CRDonepezilPlacebo
MCI0.0780.074
Mild AD0.0800.097
Statistical analysis
  • Donepezil · Posterior probability: 80.67
SecondaryChange 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.

Time frame:
Baseline, Up to Week 8
Reported as:
Mean · Proportion of correct response
Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil
Proportion of correct responseDonepezilPlacebo
Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil0.055 ± 0.078—
Statistical analysis
  • Donepezil · Posterior probability: 98.8

Adverse events

Collected over Up to Week 10 (up to 70 days). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Donepezil0/29 (0%)1/29 (3.4%)16/29 (55.2%)
Placebo0/15 (0%)0/15 (0%)4/15 (26.7%)
Most frequent serious events
Most frequent serious events
EventDonepezilPlacebo
PresyncopeNervous system disorders1/290/15
Most frequent other events
Showing 10 of 28
Most frequent other events
EventDonepezilPlacebo
DyspepsiaGastrointestinal disorders0/292/15
Upper respiratory tract infectionInfections and infestations3/290/15
Muscle spasmsMusculoskeletal and connective tissue disorders3/290/15
Abnormal dreamsPsychiatric disorders3/290/15
FatigueGeneral disorders2/291/15
Urinary tract infectionInfections and infestations2/290/15
HeadacheNervous system disorders2/291/15
Otitis mediaInfections and infestations0/291/15
DizzinessNervous system disorders0/291/15
PruritusSkin and subcutaneous tissue disorders0/291/15

Baseline characteristics

Age, Continuous
Age, Continuous(Years)DonepezilPlaceboTotal
Mean68.3 ± 7.668.4 ± 7.768.4 ± 7.5
Sex: Female, Male
Sex: Female, Male(Participants)DonepezilPlaceboTotal
Female171229
Male12315
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)DonepezilPlaceboTotal
Hispanic or Latino12719
Not Hispanic or Latino17825
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)DonepezilPlaceboTotal
American Indian or Alaska Native000
Asian101
Native Hawaiian or Other Pacific Islander000
Black or African American9615
White19928
More than one race000
Unknown or Not Reported000
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Study locations

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

Study documents

  • Protocol and statistical analysis plan · Dec 2, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 28, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04730635
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Jan 29, 2021
Start date
Mar 23, 2021
Primary completion
Jan 20, 2023
Completion
Feb 6, 2023
Results posted
Oct 28, 2024
Last update
Oct 28, 2024

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.

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