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

• ClinicalTrials.gov Identifier: NCT04730635
• Recruitment Status: Recruiting
• First Posted: January 29, 2021
• Last Update Posted: March 3, 2022
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease; Mild Cognitive Impairment	Drug: Donepezil; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Single-blind (placebo run-in) followed by double-blind
• Primary Purpose: Treatment
• Official Title: A Clinical Study to Evaluate a Cognitive Platform to Support Development of Symptomatic Therapies in Participants at Risk for Alzheimer's Disease
• Actual Study Start Date: March 23, 2021
• Estimated Primary Completion Date: January 31, 2023
• Estimated Study Completion Date: February 14, 2023

Arms and Interventions

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: MK-0000; Donepezil hydrochloride; Aricept
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.

Outcome Measures

Primary Outcome Measures :

1. Percentage Change From Baseline in Correct Responses on the One Card Learning (OCL) Task to Week 8 [ Time Frame: Baseline, Up to Week 8 ]
   OCL uses a pattern separation paradigm to assess visual memory. Tthe percentage change from baseline in correct responses on the OCL task up to Week 8 will be compared in participants receiving donepezil with participants receiving placebo.

Secondary Outcome Measures :

1. Percentage Change From Baseline in the Overall Standard Deviation (sd) in Average OCL Task (Arcsine Square Root Transformed) to Week 8 [ Time Frame: Baseline, Up to Week 8 ]
   OCL uses a pattern separation paradigm to assess visual memory. The percentage change from baseline in correct responses on the OCL task up to Week 8 will be compared in participants receiving donepezil with participants receiving placebo.
2. Percentage of Correct Responses on the OCL Task [ Time Frame: Up to approximately Week 8 ]
   OCL uses a pattern separation paradigm to assess visual memory. The percentage of correct responses on the OCL task will be compared in participants receiving donepezil with participants receiving placebo up to approximately Week 8.

Eligibility Criteria

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

Criteria

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)
• 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 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

Contacts and Locations

Contacts

Contact: Toll Free Number; 1-888-577-8839; Trialsites@merck.com

Locations

United States, California

Collaborative Neuroscience Network ( Site 0010); Recruiting

Long Beach, California, United States, 90806

Contact: Study Coordinator 562-304-1742

United States, Florida

MD Clinical ( Site 0013); Recruiting

Hallandale Beach, Florida, United States, 33009

Contact: Study Coordinator 954-455-5859

United States, Georgia

iResearch Atlanta ( Site 0005); Recruiting

Decatur, Georgia, United States, 30030

Contact: Study Coordinator 404-537-1281

United States, Louisiana

Pennington Biomedical Research Center ( Site 0006); Recruiting

Baton Rouge, Louisiana, United States, 70808

Contact: Study Coordinator 225-763-2500

United States, Ohio

Insight Clinical Trials ( Site 0020); Recruiting

Beachwood, Ohio, United States, 44122

Contact: Study Coordinator 216-832-6066

Australia, South Australia

Royal Adelaide Hospital-CALHN Memory Trials ( Site 0031); Recruiting

Adelaide, South Australia, Australia, 5000

Contact: Study Coordinator +61 8 8222 7865

Australia, Victoria

Austin Health ( Site 0030); Recruiting

Heidelberg, Victoria, Australia, 3084

Contact: Study Coordinator +61491079717

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT04730635
• Other Study ID Numbers: 0000-413; MK-0000-413 ( Other Identifier: Merck )
• First Posted: January 29, 2021
• Last Update Posted: March 3, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders; Donepezil; Cholinesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Nootropic Agents