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

NCT04730635 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 0000-413MK-0000-413
• Study Type: interventional
• Target: 44
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Outcome Measures

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.

  Baseline, Up to Week 8

Secondary Outcomes (2)

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

  Baseline, Up to Week 8

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

  Baseline, Up to Week 8

Study Arms (2)

Donepezil

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Donepezil DRUG

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

Donepezil

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (10)

Collaborative Neuroscience Network ( Site 0010)

Long Beach, California, 90806, United States

Location

Velocity Clinical Research, Hallandale Beach ( Site 0013)

Hallandale, Florida, 33009, United States

Location

Charter Research - Lady Lake ( Site 0025)

Lady Lake, Florida, 32159, United States

Location

iResearch Atlanta ( Site 0005)

Decatur, Georgia, 30030, United States

Location

iResearch Savannah ( Site 0023)

Savannah, Georgia, 31405, United States

Location

Pennington Biomedical Research Center ( Site 0006)

Baton Rouge, Louisiana, 70808, United States

Location

Insight Clinical Trials ( Site 0020)

Beachwood, Ohio, 44122, United States

Location

North Texas Clinical Trials - Fort Worth - West Rosedale ( Site 0022)

Fort Worth, Texas, 76104, United States

Location

Royal Adelaide Hospital-CALHN Memory Trials ( Site 0031)

Adelaide, South Australia, 5000, Australia

Location

Austin Health ( Site 0030)

Heidelberg, Victoria, 3084, Australia

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Single-blind (placebo run-in) followed by double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2021
• First Posted: January 29, 2021
• Study Start: March 23, 2021
• Primary Completion: January 20, 2023
• Study Completion: February 6, 2023
• Last Updated: October 28, 2024
• Results First Posted: October 28, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

US (8); AU (2)