CompletedPhase 1Results posted

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

Lead sponsor

Merck Sharp & Dohme LLC

Asset

Donepezil

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•MMSE 18-28•Study partner/caregiver required

Primary endpoint

•Averaged Correct Response Rate on the One Card Learning Task

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID0000-413

Secondary IDMK-0000-413Merck

NCT IDNCT04730635

Timeline

Milestones

Study first posted2021-01-29actual

Study start2021-03-23actual

Primary completion2023-01-20actual

Study completion2023-02-06actual

Last update posted2024-10-28actual

Results first posted2024-10-28actual

Assets

Drug assets

Donepezil

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (6)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Memory

6 endpoints

Primary/protocol endpoint

Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Primary/registry result

Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Posted result

Group	Value (mean), Proportion of correct response	Standard deviation
Donepeziln=23 Participants	0.055	0.078
Placebon=13 Participants	0.034	0.091

Posterior Probability46.30

There was a threshold of ≥2 percentage points. A posterior probability value \>55% was required to satisfy the primary hypothesis.

Secondary/protocol endpoint

Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Secondary/registry result

Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Posted result

Group	Value (number), Arcsine sqrt transformed proportion CR	Reported bounds
DonepezilMCIn=16 Participants	0.078	-
Mild ADn=7 Participants	0.080	-
PlaceboMCIn=9 Participants	0.074	-
Mild ADn=4 Participants	0.097	-

Posterior Probability80.67

There was a threshold of ≤ 0.1 for this standard deviation change. A posterior probability value \>70% was required to satisfy this secondary hypothesis.

Secondary/registry result

Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil

Time frame:Baseline, Up to Week 8

change from baseline, improvement

Posted result

Group	Value (mean), Proportion of correct response	Standard deviation
Donepeziln=23 Participants	0.055	0.078

Posterior Probability98.8

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.