Alzheimer's DiseasePhase 1NCT04730635
Cognition Platform Study in Participants at Risk for Alzheimer's Disease (AD) (MK-0000-413)
A Phase 1 study testing Donepezil in people with Alzheimer's Disease and Mild Cognitive Impairment, run by Merck Sharp & Dohme LLC at 10 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 55 to 85 years
- Conditions the study is for
- Alzheimer's Disease, Mild Cognitive Impairment
- What is being tested?
- Donepezil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 23 Mar 2021to 6 Feb 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States8 sites
Pennington Biomedical Research Center ( Site 0006)
Baton Rouge, Louisiana, 70808
Insight Clinical Trials ( Site 0020)
Beachwood, Ohio, 44122
iResearch Atlanta ( Site 0005)
Decatur, Georgia, 30030
North Texas Clinical Trials - Fort Worth - West Rosedale ( Site 0022)
Fort Worth, Texas, 76104
Velocity Clinical Research, Hallandale Beach ( Site 0013)
Hallandale, Florida, 33009
Charter Research - Lady Lake ( Site 0025)
Lady Lake, Florida, 32159
Collaborative Neuroscience Network ( Site 0010)
Long Beach, California, 90806
iResearch Savannah ( Site 0023)
Savannah, Georgia, 31405
Australia2 sites
Royal Adelaide Hospital-CALHN Memory Trials ( Site 0031)
Adelaide, South Australia, 5000
Austin Health ( Site 0030)
Heidelberg, Victoria, 3084
About this study
Official title: 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.
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- Being tested
- Donepezil, Placebo
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called MK-0000, Donepezil hydrochloride, Aricept
Donepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56.
PlaceboDrug
Dose matched placebo capsule QD, orally for Days 1-56.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Donepezil |
| Placebo | Placebo comparator | Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: Baseline, Up to Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start23 Mar 2021
- Primary completion20 Jan 2023
- Study completion6 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730635
- Sponsor's protocol ID
- 0000-413
- Other IDs
- MK-0000-413
- Status last verified
- Jul 2024
- First submitted
- 26 Jan 2021
- Last updated
- 28 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study to Evaluate a Cognitive Platform to Support Development of Symptomatic Therapies in Participants at Risk for Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT04730635
- Acronym / sponsor ID
- 0000-413
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 20 Jan 2023 (actual)
- Study completion
- 6 Feb 2023 (actual)
- First posted
- 29 Jan 2021 (actual)
- Results
- Posted 28 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Experimental | Drug: DonepezilParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DonepezilAlso: MK-0000, Donepezil hydrochloride, AriceptDonepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56. | Drug | Donepezil |
| PlaceboDose matched placebo capsule QD, orally for Days 1-56. | Drug | Placebo |
Primary outcome
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8
Time frame: Baseline, Up 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.
2 secondary outcomes
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 in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil
Time frame: Baseline, Up to Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Donepezil in people with Alzheimer's Disease and Mild Cognitive Impairment, run by Merck Sharp & Dohme LLC at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8 (time frame: Baseline, Up to Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024; AzTrials last refreshed its copy on 6 Nov 2026.