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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of multiple ascending doses of MK-8189 in participants with Alzheimer's Disease (AD) with or without symptoms of agitation-aggression and/or psychosis.

Official Title
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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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: MK-8189
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-8189<br>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: MK-8189<br>* MK-8189 administered orally once a day (QD) at a titration via tablet in 4 mg and 12 mg dose strengths<br>|
| Placebo Comparator: Placebo<br>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<br>* MK-8189 matching placebo administered orally QD<br>|

What is the study measuring?
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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. The number of participants who experienced an AE will be reported. | Up to approximately 42 days | 
| Number of participants discontinuing study treatment due to 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. The number of participants who discontinued study treatment due to an AE will be reported. | Up to approximately 28 days |