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Efficacy and Safety of MK-1167 in Participants With Alzheimer's Disease Dementia Taking Stable Donepezil Treatment (MK-1167-007)

Phase 1
Active, not recruiting
Conditions
Alzheimer's Disease
Interventions
Registration Number
NCT06285240
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

The main purpose of this study is to assess the safety and efficacy of MK-1167 administered to participants with Alzheimer's Disease (AD) receiving stable Donepezil treatment.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
28
Inclusion Criteria
  • Reports 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 subject well or is documented in medical records
  • Meets the criteria for a diagnosis of probable Alzheimer's disease (AD) based on the National Institute of Neurological and Communicative Disorders - Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD
  • Is receiving donepezil 10 mg daily for symptomatic treatment of cognitive impairment associated with AD. The dose level must be stable for at least 2 months prior to Screening. If receiving donepezil via a transdermal system (ie, patch), it should be a 10-mg/day dose and should switch prescription to a 10-mg oral daily dose, before enrollment
  • Has a reliable and competent trial partner/caregiver who has a close relationship with the participant, has face-to-face contact at least 3 days a week for a minimum of 6 waking hours a week, and is willing to accompany the participant, if desired, to study visits
Exclusion Criteria
  • History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases that are not under medical control over the past 2 months.
  • Has evidence of a clinically relevant or unstable psychiatric disorder, based on DSM-5 criteria, or has a history of clinically significant psychiatric disorder in the last 5 years. Generalized anxiety disorder, and/or insomnia under good control for ≥ 2 months on stable medical therapy may not be exclusionary.
  • History of cancer (malignancy). Participants with adequately treated disease deemed as "cured," or who, in the opinion of the study investigator, are highly unlikely to sustain a recurrence for the duration of the study, may be enrolled at the discretion of the investigator and Sponsor.
  • History of significant multiple and/or severe allergies (eg, food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (ie, systemic allergic reaction) to prescription or nonprescription drugs or food.
  • Had a major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the prestudy (screening) visit.
  • Unable to refrain from or anticipates the use of any medication, including prescription and nonprescription drugs or herbal remedies beginning approximately 2 weeks (or 5 half-lives) prior to administration of the initial dose of study intervention, throughout the study, until the poststudy visit. There may be certain protocol-specified medications that are permitted.
  • The participant is a smoker and/or has used nicotine or nicotine-containing products (eg, nicotine patch and electronic cigarette) within 3 months of screening.
  • Consumes greater than 3 servings of alcoholic beverages per day. Participants who consume 4 servings of alcoholic beverages per day may be enrolled at the discretion of the investigator.
  • The participant is a regular user of cannabis, any illicit drugs or has a history of drug (including alcohol) abuse within approximately 2 years.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MK-1167 Panel BMK-1167Participants receive 6 mg MK-1167 oral doses QD Days 1 to 31. Participants also receive 10 mg oral Donepezil on Days -3 to 31.
MK-1167 Panel AMK-1167Participants receive 6 mg MK-1167 oral loading doses QD Days 1 to 7, followed by 3 mg MK-1167 oral maintenance doses QD Days 8 to 21. Participants also receive 10 mg oral Donepezil on Days -3 to 21.
MK-1167 Panel ADonepezilParticipants receive 6 mg MK-1167 oral loading doses QD Days 1 to 7, followed by 3 mg MK-1167 oral maintenance doses QD Days 8 to 21. Participants also receive 10 mg oral Donepezil on Days -3 to 21.
Placebo Panel ADonepezilParticipants receive placebo to MK-1167 oral QD from Days 1 to 21. Participants also receive 10 mg oral Donepezil QD on Days -3 to 21
Placebo Panel APlaceboParticipants receive placebo to MK-1167 oral QD from Days 1 to 21. Participants also receive 10 mg oral Donepezil QD on Days -3 to 21
MK-1167 Panel BDonepezilParticipants receive 6 mg MK-1167 oral doses QD Days 1 to 31. Participants also receive 10 mg oral Donepezil on Days -3 to 31.
Placebo Panel BPlaceboParticipants receive placebo to MK-1167 oral QD from Days 1 to 31. Participants also receive 10 mg oral Donepezil QD on Days -3 to 31.
Placebo Panel BDonepezilParticipants receive placebo to MK-1167 oral QD from Days 1 to 31. Participants also receive 10 mg oral Donepezil QD on Days -3 to 31.
Primary Outcome Measures
NameTimeMethod
Number of participants experiencing an Adverse Event (AE)Up to approximately 7 weeks

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.

Number of participants discontinuing study treatment due to an AEUp to approximately 4 weeks

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 discontinue study treatment due to an AE will be reported.

Secondary Outcome Measures
NameTimeMethod
Apparent Terminal Half-Life (t½) of MK-1167At designated time points up to day 51

Apparent t½ is the time required for a given drug concentration in the plasma to decrease by 50%.

Oral Clearance (CL/F) of MK-1167 from PlasmaAt designated time points up to day 51

CL/F is defined as the rate at which MK-6552 is completely removed from plasma.

Maximum Plasma Concentration (Cmax) of MK-1167At designated time points up to day 31

Cmax is a measure of the maximum amount of drug in the plasma after the dose is given.

Plasma Concentration at 24 hours postdose (C24)At designated time points up to day 31

Plasma concentration of MK-1167 at 24 hours (C24) will be reported.

Time to Reach Maximum Plasma Concentration (Tmax) of MK-1167At designated time points up to day 51

Tmax is a measure of the time to reach the maximum concentration in plasma after the drug dose.

Apparent Volume of Distribution (Vz/F) of MK-1167At designated time points up to day 51

Vz/F is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.

Area Under the Plasma Concentration-Time Curve from Dosing to 24 Hours Postdose (AUC0-24) of MK-1167At designated time points up to day 31

AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24.

Trial Locations

Locations (3)

Velocity Clinical Research, Hallandale Beach ( Site 0001)

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Hallandale Beach, Florida, United States

CenExel iResearch, LLC ( Site 0003)

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Decatur, Georgia, United States

CenExel iResearch, LLC ( Site 0004)

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Savannah, Georgia, United States

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