This study will evaluate the safety, tolerability, and pharmacokinetics of MK-4334 administered once daily (QD) in participants with Alzheimer's clinical syndrome receiving a stable, daily dose of donepezil 10 mg, taken orally (PO). This includes participants with symptoms of mild cognitive impairment (MCI) or mild to moderate Alzheimer's disease (AD). It is hypothesized that the true geometric mean minimum plasma concentration at 24 hours (C24) is at least 60 nM at steady state in the presence of steady-state donepezil 10 mg.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive MK-4334 capsules administered orally, QD on Days 1-14. Participants will receive an initial loading dose of 120 mg (Day 1), followed by a maintenance dose of 60 mg (Days 2-14). Open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14.
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD)will receive placebo capsules matching MK-4334 administered orally, QD on Days 1-14. Participants will also receive open-label donepezil tablets (dose strength: 10 mg) administered orally, QD on Days 1-14.
Participants with Alzheimer's clinical syndrome (MCI or mild/moderate AD) will receive open-label, oral donepezil 10 mg QD on Days 1-14.
Number of Participants Experiencing an Adverse Event (AE)
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study treatment. For each arm, the number of participants experiencing an AE will be assessed.
Time frame: Up to 42 days
Number of Participants Discontinuing Study Treatment due to an Adverse Event
An AE is any unfavorable and unintended sign, symptom, or disease (new or exacerbated) in a clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. For each arm, the number of participants discontinuing study treatment due to an AE will be assessed.
Time frame: Up to 14 days
Plasma Steady State Concentration at 24 Hours (C24) of MK-4334
Plasma steady state concentration at 24 hours (C24) will be reported.
Time frame: Day 14: Pre-dose and 24 hours after MK-4334 administration
Plasma Steady State Area Under the Concentration-Time Curve from 0 to 24 hours (AUC0-24) of MK-4334
Plasma steady state area under the concentration-time curve from 0 to 24 hours (AUC0-24) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours after MK-4334 administration
Plasma Steady State Maximum Concentration (Cmax) of MK-4334
Plasma steady state maximum concentration (Cmax) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Half-Life (t1/2) of MK-4334
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Plasma steady state apparent half-life (t1/2) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Time to Maximum Concentration (Tmax) of MK-4334
Plasma steady state time to maximum concentration (Tmax) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Clearance (CL/F) of MK-4334
Plasma steady state apparent clearance (CL/F) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration
Plasma Steady State Apparent Volume of Distribution (Vz/F) of MK-4334
Plasma steady state apparent volume of distribution (Vz/F) will be reported.
Time frame: Day 14: Pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360, and 480 hours after MK-4334 administration