Elpipodect (MK-8189) Safety and Tolerability in Participants With Alzheimer's Disease With or Without Symptoms of Agitation-Aggression and/or Psychosis (MK-8189-017)

A Randomized Clinical Study to Evaluate the Safety and Tolerability of MK-8189 in Participants With Alzheimer's Disease With or Without Symptoms of Agitation-Aggression and/or Psychosis

The purpose of this study is to evaluate the safety and tolerability of multiple ascending doses of elpipodect in participants with Alzheimer's Disease (AD) with or without symptoms of agitation-aggression and/or psychosis.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Placebo; Drug: Elpipodect

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Ana, California, United States, 92705
      • CITrials ( Site 0007)
  • Florida
    • Cutler Bay, Florida, United States, 33189
      • Top Medical Research ( Site 0005)
    • Hallandale, Florida, United States, 33009
      • Velocity Clinical Research, Hallandale Beach ( Site 0001)
    • Miami, Florida, United States, 33173
      • Well Pharma Medical Research, Corp. ( Site 0006)
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research ( Site 0004)
    • Decatur, Georgia, United States, 30030
      • iResearch Atlanta ( Site 0009)
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute ( Site 0008)
  • New York
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates ( Site 0003)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 85 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has a documented diagnosis of probable Alzheimer Disease based on National Institute on Aging-Alzheimer Association criteria for AD, with a history of cognitive and functional decline with gradual onset and slow progression for at least 1 year before screening, that is either corroborated by an informant who knows the participant well or is documented in medical records
• Lives in the community setting with a reliable trial partner/caregiver or lives alone in an assisted living facility, with supervision and has a reliable trial partner/caregiver
• Has a reliable and competent trial partner/caregiver who must have a close relationship with the participant and is knowledgeable of the participant's condition and progress and able to read, understand and speak the designated language at the study site
• Can read at the 6th grade level/equivalent as determined by the investigator
• Has an academic and/or employment history sufficient to exclude intellectual disability and is able, in the opinion of the investigator, to fully participate in the study
• Participants receiving treatment with a cholinesterase inhibitor or other treatment for AD, must have been on a stable regimen for 3 months prior to screening and there are no expected changes in co-medication during the study
• Is able to discontinue any antipsychotic medication they are taking at the time of Screening
• Has a body mass index (BMI) > 18 and ≤ 35kg/m2, inclusive

Exclusion Criteria:

• Has agitation/aggression or psychosis that is attributable to concomitant medications, environmental conditions, substance abuse, or an active medical or psychiatric condition
• Has a known history of stroke or evidence from prior magnetic resonance imaging (MRI) scan (if available) that is clinically important in the investigator's opinion
• Has evidence of a clinically relevant neurological disorder other than the disease being studied (i.e., probable AD) at Screening
• Has a history of seizures or epilepsy within the last 5 years before Screening
• Has evidence of a clinically relevant or unstable psychiatric disorder
• Is at imminent risk of self-harm
• Has a history of alcoholism or drug dependency/abuse within the last 5 years before Screening
• Has a history of cancer (malignancy). Exceptions: (1) Adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or; (2) Other malignancies that have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study
• Has a family history of long QT syndrome
• Previously developed severe extrapyramidal symptoms (EPS) following administration of any prescribed medication or study treatment
• Is positive for hepatitis B surface antigen (HBsAg), 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 pre-study (screening) visit
• Consumes greater than 3 glasses of alcoholic beverages per day
• Consumes excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) 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 3 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will be assigned to one of the following regimens: Titration 1: 2 tablets Days 1-28 OR Titration 2: 2 tablets Days 1-28 OR Titration 3: 1 tablet Days 1-3; 2 tablets Days 4-28.	Drug: Placebo; MK-8189 matching placebo administered orally QD
Experimental: Elpipodect; Participants will be assigned to one of the following regimens: Titration 1: 4 mg x 2 tablets Days 1-3; 4 mg x 1 tablet & 12 mg x 1 tablet Days 4-28 OR Titration 2: 4 mg x 2 tablets Days 1-3; 4 mg x 1 tablet & 12 mg x 1 tablet Days 4-6; 12 mg x 2 tablets Days 7-28 OR Titration 3: 4 mg x 1 tablet Days 1-3; 4 mg x 2 tablets Days 4-6; 4 mg x 1 tablet & 12 mg x 1 tablet Days 7-9; 12 mg x 2 tablets Days 10-28.	Drug: Elpipodect; MK-8189 administered orally once a day (QD) at a titration via tablet in 4 mg and 12 mg dose strengths; Other Names: MK-8189

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose.	Up to approximately 42 days
Number of Participants Discontinuing From Study Therapy Due to AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Results are reported according to dose.	Up to approximately 42 days

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Actual): January 10, 2023
• Study Completion (Actual): January 10, 2023

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; MK-8189
• Other Study ID Numbers: 8189-017; MK-8189-017 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No