WithdrawnPhase 1

Multiple Dose Trial of MK-4334 in Participants With Alzheimer's Clinical Syndrome (MK-4334-005)

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

Lead sponsor

Merck Sharp & Dohme LLC

Assets

Donepezil / MK-4334

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•mild AD dementia•MMSE 12-24•AD symptomatic therapy: stable

Primary endpoints

•Adverse Event (AE)•Number of Participants Discontinuing Study Treatment due to an Adverse Event

Identifiers

Registered as

Org study ID4334-005

Secondary IDMK-4334-005Merck Protocol Number

NCT IDNCT03740178

Timeline

Milestones

Study first posted2018-11-14actual

Study start2019-09-27estimated

Primary completion2020-02-28estimated

Study completion2020-02-28estimated

Last update posted2025-04-25actual

Assets

Drug assets

Donepezil MK-4334

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

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

•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

Exclusion criteria

•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.

•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.

Endpoints (9)

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.

Coverage by outcome category

Safety / tolerability / PK

Other (unclassified)

Safety / tolerability / PK

5 endpoints

Primary/protocol endpoint

Number of Participants Experiencing an Adverse Event (AE)

Time frame:Up to 42 days

event count, event

Primary/protocol endpoint

Number of Participants Discontinuing Study Treatment due to an Adverse Event

Time frame:Up to 14 days

event count, event

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

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

concentration, descriptive

Secondary/protocol endpoint

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

time to event, event

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Plasma Steady State Concentration at 24 Hours (C24) of MK-4334

Time frame:Day 14: Pre-dose and 24 hours after MK-4334 administration

concentration, descriptive

Secondary/protocol endpoint/low confidence

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

concentration, descriptive

Secondary/protocol endpoint/low confidence

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

descriptive

Secondary/protocol endpoint/low confidence

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

descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableno registry results posted yet

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.