Clinical trial NCT06285240: Efficacy and Safety of MK-1167 in Participants With Alzheimer's Disease Dementia Taking Stable Donepezil Treatment (MK-1167-007)
Official title: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Assess the Safety, Tolerability, and Pharmacokinetics of MK-1167 Administered to Patients With Alzheimer's Disease Receiving Stable Donepezil Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2024-02-29
Enrollment: 28
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Panel A participants will receive a loading dose of MK-1167 6 mg or matching Placebo on Days 1 to 7 followed by once daily (QD) dosing of MK-1167 3 mg or matching Placebo for 14 consecutive days (Days 8 to 21). Panel B participants will receive QD dosing of MK-1167 6 mg or matching Placebo for Days 1 to 31. Panel B will be initiated following review of safety and tolerability data from Panel A.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants experiencing an Adverse Event (AE)
timeFrame: Up to approximately 7 weeks
measure: Number of participants discontinuing study treatment due to an AE
timeFrame: Up to approximately 4 weeks
Secondary outcomes:
measure: Area Under the Plasma Concentration-Time Curve from Dosing to 24 Hours Postdose (AUC0-24) of MK-1167
timeFrame: At designated time points up to day 31
measure: Maximum Plasma Concentration (Cmax) of MK-1167
timeFrame: At designated time points up to day 31
measure: Plasma Concentration at 24 hours postdose (C24)
timeFrame: At designated time points up to day 31
measure: Time to Reach Maximum Plasma Concentration (Tmax) of MK-1167
timeFrame: At designated time points up to day 51
measure: Apparent Terminal Half-Life (t½) of MK-1167
timeFrame: At designated time points up to day 51
measure: Oral Clearance (CL/F) of MK-1167 from Plasma
timeFrame: At designated time points up to day 51
measure: Apparent Volume of Distribution (Vz/F) of MK-1167
timeFrame: At designated time points up to day 51
Other outcomes:
Locations:
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach ( Site 0001)
state: Florida
city: Decatur
country: United States
facility: CenExel iResearch, LLC ( Site 0003)
state: Georgia
city: Savannah
country: United States
facility: CenExel iResearch, LLC ( Site 0004)
state: Georgia
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: