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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: Donepezil; Drug: Placebo; Drug: MK-1167

Study type: Interventional

Funder types: Industry

Identifiers

NCT06285240

MK-1167-007 (Other Identifier)

1167-007

Details and patient eligibility

About

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.

Enrollment: 28 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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28 participants in 4 patient groups, including a placebo group

MK-1167 Panel A

Experimental group

Description:

Participants 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.

Treatment:

Drug: MK-1167

Drug: Donepezil

Placebo Panel A

Placebo Comparator group

Description:

Participants 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

Treatment:

Drug: Placebo

Drug: Donepezil

MK-1167 Panel B

Experimental group

Description:

Participants receive 6 mg MK-1167 oral doses QD Days 1 to 31. Participants also receive 10 mg oral Donepezil on Days -3 to 31.

Treatment:

Drug: MK-1167

Drug: Donepezil

Placebo Panel B

Placebo Comparator group

Description:

Participants 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.

Treatment:

Drug: Placebo

Drug: Donepezil