Alzheimer's DiseasePhase 1NCT03740178
Multiple Dose Trial of MK-4334 in Participants With Alzheimer's Clinical Syndrome (MK-4334-005)
A Phase 1 study testing MK-4334 and Donepepzil in people with Alzheimer's Disease and Mild Cognitive Impairment, run by Merck Sharp & Dohme LLC.
Trial summary
This study will evaluate the safety, tolerability, and pharmacokinetics of MK-4334 administered once daily (QD) in participants with Alzheimer's clinical syndrome receiving a stable, daily dose of donepezil 10 mg, taken orally (PO). 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?
- MK-4334 and Donepepzil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 27 Sep 2019to 28 Feb 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Participants with MCI
- Have a history of subjective memory decline with gradual onset and slow progression for at least one year before screening.
- Have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia based on National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
- Have a Mini Mental State Exam-2 (MMSE-2) score ≥24.
- Have a Clinical Dementia Rating (CDR) scale score of 0.5, including a memory subscale score ≥ 0.5.
- Participants with AD
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- Have a history of cognitive and functional decline with gradual onset and slow progression for at least one year before screening.
- Meet the criteria for a diagnosis of probable AD based on NINCDS-ADRDA criteria.
- Have a MMSE-2 score ≥ 12 to ≤ 24 at screening.
- Have a CDR score of 1 to 2.
- All Participants
- Have a Rosen-Modified Hachinski score ≤ 4.
- Be on a stable dose of donepezil 10 mg PO daily for symptomatic treatment of Alzheimer's clinical syndrome. The dose must be stable for ≥2 months prior to screening.
- Be in good health based on medical history, physical examination, vital sign (VS) measurements and electrocardiograms (ECGs) performed prior to randomization.
- Have a Body Mass Index (BMI) ≤ 35 kg/m^2.
- If female, is a woman of non-childbearing potential (WONCBP).
- If male, must agree to either remain abstinent or use contraception during the intervention period and for ≥28 days after the last dose of study intervention.
- Have acceptable venous access.
Who cannot join
- Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator.
- Has a history of uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- Has evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, or delirium, at the time of prestudy (screening) visit, or has a history of clinically significant psychiatric disorder of the last 5 years.
- Has a history of cancer (malignancy), except for: 1.) adequately-treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2.) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study.
- Participant has an estimated creatinine clearance (CrCl) ≤55 mL/min based on the Modification of Diet in Renal Disease (MDRD).
- Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food.
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- Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV).
- Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
- Is unable to refrain from or anticipates the use of strong or moderate inhibitors or inducers of Cytochrome P450 (CYP) 3A4 (CYP3A4) and CYP2C19 beginning approximately 28 days prior to administration of the initial dose of study drug, throughout the study, and until the post-trial visit.
- Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the prestudy (screening) visit.
- Has a rate-corrected QT (QTc) interval ≥470 msec (for males) or ≥480 msec (for females).
- Is a smoker and/or has used nicotine or nicotine-containing products (e.g., nicotine patch and electronic cigarette) within 3 months of screening.
- Consumes greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer [354 mL/12 ounces], wine [118 mL/4 ounces], or distilled spirits [29.5 mL/1 ounce]) 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 (including alcohol) abuse within approximately 2 years. Participants must have a negative urine drug screen prior to randomization.
About this study
Official title: A Randomized, Double-Blinded Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of MK-4334 in Participants With Alzheimer's Clinical Syndrome on a Stable Dose of Donepezil
This study will evaluate the safety, tolerability, and pharmacokinetics of MK-4334 administered once daily (QD) in participants with Alzheimer's clinical syndrome receiving a stable, daily dose of donepezil 10 mg, taken orally (PO). This includes participants with symptoms of mild cognitive impairment (MCI) or mild to moderate Alzheimer's disease (AD). It is hypothesized that the true geometric mean minimum plasma concentration at 24 hours (C24) is at least 60 nM at steady state in the presence of steady-state donepezil 10 mg.
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- Being tested
- MK-4334, Placebo to MK-4334, Donepepzil
- 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.
MK-4334Drug
Also called Aricept
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive MK-4334 capsules administered orally, QD on Days 1-14. Participants will receive an initial loading dose of 120 mg (Day 1), followed by a maintenance dose of 60 mg (Days 2-14). Open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14.
Placebo to MK-4334Drug
Also called Aricept
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD)will receive placebo capsules matching MK-4334 administered orally, QD on Days 1-14. Participants will also receive open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14.
DonepepzilDrug
Also called Aricept
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive open-label, oral donepezil 10 mg QD on Days 1-14.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil + MK-4334 | Experimental | Oral MK-4334 60/120 mg QD and open-label, oral donepezil 10 mg QD. Receives: Drug: MK-4334; Drug: Donepepzil |
| Donepezil + Placebo | Placebo comparator | Placebo to MK-4334 QD and open-label, oral donepezil 10 mg QD. Receives: Drug: Placebo to MK-4334; Drug: Donepepzil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Experiencing an Adverse Event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
Measured: Up to 42 days
Number of Participants Discontinuing Study Treatment due to an Adverse Event
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE will be assessed.
Measured: Up to 14 days
Secondary outcomes (7)
Plasma Steady State Concentration at 24 Hours (C24) of MK-4334
Plasma steady state concentration at 24 hours (C24) will be reported.
Measured: Day 14: Pre-dose and 24 hours after MK-4334 administration
Plasma Steady State Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of MK-4334
Plasma steady state area under the concentration-time curve from 0 to 24 hours (AUC0-24) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after MK-4334 administration
Plasma Steady State Maximum Concentration (Cmax) of MK-4334
Plasma steady state maximum concentration (Cmax) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Half-Life (t1/2) of MK-4334
Plasma steady state apparent half-life (t1/2) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Time to Maximum Concentration (Tmax) of MK-4334
Plasma steady state time to maximum concentration (Tmax) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Clearance (CL/F) of MK-4334
Plasma steady state apparent clearance (CL/F) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Volume of Distribution (Vz/F) of MK-4334
Plasma steady state apparent volume of distribution (Vz/F) will be reported.
Measured: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2018
- Study start27 Sep 2019 (estimated)
- Primary completion28 Feb 2020 (estimated)
- Study completion28 Feb 2020 (estimated)
Why it stopped: Development program discontinuation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- None (open label)
- Enrolment
- 0 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
- NCT03740178
- Sponsor's protocol ID
- 4334-005
- Other IDs
- MK-4334-005
- Status last verified
- Apr 2025
- First submitted
- 12 Nov 2018
- Last updated
- 25 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded Clinical Trial to Assess the Safety, Tolerability and Pharmacokinetics of MK-4334 in Participants With Alzheimer's Clinical Syndrome on a Stable Dose of Donepezil
- ClinicalTrials.gov ID
- NCT03740178
- Acronym / sponsor ID
- 4334-005
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Development program discontinuation
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 27 Sep 2019 (estimated)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 28 Feb 2020 (estimated)
- First posted
- 14 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety, tolerability, and pharmacokinetics of MK-4334 administered once daily (QD) in participants with Alzheimer's clinical syndrome receiving a stable, daily dose of donepezil 10 mg, taken orally (PO). This includes participants with symptoms of mild cognitive impairment (MCI) or mild to moderate Alzheimer's disease (AD). It is hypothesized that the true geometric mean minimum plasma concentration at 24 hours (C24) is at least 60 nM at steady state in the presence of steady-state donepezil 10 mg.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil + MK-4334 | Experimental | Drug: MK-4334, Drug: DonepepzilOral MK-4334 60/120 mg QD and open-label, oral donepezil 10 mg QD. |
| Donepezil + Placebo | Placebo comparator | Drug: Placebo to MK-4334, Drug: DonepepzilPlacebo to MK-4334 QD and open-label, oral donepezil 10 mg QD. |
Who may qualify
- Ages
- 55 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Participants with MCI
- Have a history of subjective memory decline with gradual onset and slow progression for at least one year before screening.
- Have general cognitive function and activities of daily living sufficiently intact, based on clinical assessment, so as not to meet criteria for mild AD dementia based on National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria.
- Have a Mini Mental State Exam-2 (MMSE-2) score ≥24.
- Have a Clinical Dementia Rating (CDR) scale score of 0.5, including a memory subscale score ≥ 0.5.
Key exclusion criteria (15 listed)
- Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (C-SSRS), or of harm to others in the opinion of the investigator.
- Has a history of uncontrolled endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases.
- Has evidence of a clinically relevant or unstable psychiatric disorder, based on Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, or delirium, at the time of prestudy (screening) visit, or has a history of clinically significant psychiatric disorder of the last 5 years.
- Has a history of cancer (malignancy), except for: 1.) adequately-treated nonmelanomatous skin carcinoma or carcinoma in situ of the cervix or; 2.) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study.
- Participant has an estimated creatinine clearance (CrCl) ≤55 mL/min based on the Modification of Diet in Renal Disease (MDRD).
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 |
|---|---|---|
| MK-4334Also: AriceptParticipants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive MK-4334 capsules administered orally, QD on Days 1-14. Participants will receive an initial loading dose of 120 mg (Day 1), followed by a maintenance dose of 60 mg (Days 2-14). Open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14. | Drug | Donepezil + MK-4334 |
| Placebo to MK-4334Also: AriceptParticipants with Alzheimer's clinical syndrome (MCI or mild/moderate AD)will receive placebo capsules matching MK-4334 administered orally, QD on Days 1-14. Participants will also receive open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14. | Drug | Donepezil + Placebo |
| DonepepzilAlso: AriceptParticipants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive open-label, oral donepezil 10 mg QD on Days 1-14. | Drug | Donepezil + MK-4334, Donepezil + Placebo |
Primary outcome
Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to 42 days
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
Number of Participants Discontinuing Study Treatment due to an Adverse Event
Time frame: Up to 14 days
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE will be assessed.
7 secondary outcomes
Plasma Steady State Concentration at 24 Hours (C24) of MK-4334
Time frame: Day 14: Pre-dose and 24 hours after MK-4334 administration
Plasma Steady State Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after MK-4334 administration
Plasma Steady State Maximum Concentration (Cmax) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Half-Life (t1/2) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Time to Maximum Concentration (Tmax) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Clearance (CL/F) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Volume of Distribution (Vz/F) of MK-4334
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2025.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/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
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-4334 and Donepepzil in people with Alzheimer's Disease and Mild Cognitive Impairment, run by Merck Sharp & Dohme LLC.
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 18 inclusion and 15 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: withdrawn, as of the sponsor's last update on 25 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of Participants Experiencing an Adverse Event (AE) (time frame: Up to 42 days). The study lists 2 primary outcomes in all. 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 25 Apr 2025.