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

Merck Sharp & Dohme LLC28 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Alzheimer's Disease

Interventions

MK-1167DRUG

1 mg and 5 mg oral capsules

DonepezilDRUG

10 mg oral tablets

PlaceboDRUG

MK-1167 matching placebo administered oral capsules

Eligibility

Sex: ALLMin age: 50 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (3)

Velocity Clinical Research, Hallandale Beach ( Site 0001)

Hallandale, Florida, United States

CenExel iResearch, LLC ( Site 0003)

Decatur, Georgia, United States

CenExel iResearch, LLC ( Site 0004)

Savannah, Georgia, United States

Outcomes

Primary Outcomes

Number of Participants Who Experienced an Adverse Event (AE)

An AE was 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 were reported.

Time frame: Up to approximately 7 weeks

Number of Participants Who Discontinued Study Treatment Due to an AE

Time frame: Up to approximately 4 weeks

Secondary Outcomes

Panel A: Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours (AUC0-24) After Administration of 6mg of MK-1167

AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel A participants after administration of 6mg of MK-1167.

Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: AUC0-24 After Administration of 3mg of MK-1167

AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC 0-24 value was presented for Panel A participants after administration of 3mg of MK-1167.

Data from ClinicalTrials.gov

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Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: AUC0-24 After Administration of 6mg of MK-1167

AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Blood samples were collected at pre-specified intervals for the determination of AUC0-24. Per protocol, AUC0-24 was based on noncompartmental analysis, and a geometric mean AUC0-24 value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Maximum Plasma Concentration (Cmax) After Administration of 6mg of MK-1167

Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel A participants after administration of 6mg of MK-1167.

Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Cmax After Administration of 3mg of MK-1167

Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Cmax After Administration of 6mg of MK-1167

Cmax was defined as the maximum serum concentration of MK-1167 reached. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, Cmax was based on noncompartmental analysis, and a geometric mean Cmax value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Plasma Concentration at 24 Hours (C24) After Administration of 6mg of MK-1167

C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel A participants after administration of 6mg of MK-1167.

Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: C24 After Administration of 3mg of MK-1167

Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: C24 After Administration of 6mg of MK-1167

C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Per protocol, C24 was based on noncompartmental analysis, and a geometric mean C24 value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Time to Maximum Plasma Concentration (Tmax) After Administration of 6mg of MK-1167

Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel A participants after administration of 6mg of MK-1167.

Time frame: Day 1: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Tmax After Administration of 3mg of MK-1167

Time frame: Days 8, 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Tmax After Administration of 6mg of MK-1167

Tmax was defined as time to the maximum concentration of MK-1167 reached. Blood samples were collected at pre-specified intervals for the determination of Tmax. Per protocol, Tmax was based on noncompartmental analysis, and a median Tmax value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Days 1, 23, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel A: Apparent Clearance (CL/F) After Administration of 3mg of MK-1167

CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel A participants after administration of 3mg of MK-1167.

Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel B: CL/F After Administration of 6mg of MK-1167

CL/F is the rate at which the MK-1167 is completely removed from plasma. Blood samples were collected at pre-specified intervals for the determination of CL/F. Per protocol, CL/F was based on noncompartmental analysis, and a geometric mean CL/F value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel A: Apparent Terminal Half-Life (t1/2) After Administration of 3mg of MK-1167

t1/2 is defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified intervals for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel A participants after administration of 3mg of MK-1167.

Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel B: t1/2 After Administration of 6mg of MK-1167

t1/2 was defined as the time required to divide plasma concentration of MK-1167 by half after reaching pseudo-equilibrium. Blood samples were collected at pre-specified timepoints for the determination of t1/2. Per protocol, t1/2 was based on noncompartmental analysis, and a geometric mean t1/2 value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel A: Apparent Volume of Distribution (Vz/F) After Administration of 3mg of MK-1167

Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel A participants after administration of 3mg of MK-1167.

Time frame: Day 21: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel B: Vz/F After Administration of 6mg of MK-1167

Vz/F was the apparent volume of distribution of MK-1167. Blood samples were collected at pre-specified intervals for the determination of Vz/F. Per protocol, Vz/F was based on noncompartmental analysis, and a geometric mean Vz/F value was presented for Panel B participants after administration of 6mg of MK-1167.

Time frame: Day 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 120, 240, 360 and 480 hours postdose

Panel B: Day 23 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 23. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 AUC0-24/Day 1 AUC0-24.

Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Day 31 to Day 1 Accumulation Ratio of AUC0-24 After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine AUC0-24 on Days 1 and 31. AUC0-24 was defined as the area under the concentration-time curve of MK-1167 from time zero to 24 hours. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 AUC0-24/Day 1 AUC0-24.

Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Day 23 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 23. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 Cmax/Day 1 Cmax.

Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Day 31 to Day 1 Accumulation Ratio of Cmax After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine Cmax on Days 1 and 31. Cmax was defined as the maximum serum concentration of MK-1167 reached. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 Cmax/Day 1 Cmax.

Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Day 23 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 23. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 23 to Day 1 was calculated as Day 23 C24/Day 1 C24.

Time frame: Days 1, 23: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Panel B: Day 31 to Day 1 Accumulation Ratio of C24 After Administration of 6mg of MK-1167

Blood samples were collected at pre-specified timepoints to determine C24 on Days 1 and 31. C24 was defined as the serum concentration of MK-1167 reached at 24 hours. Blood samples were collected at pre-specified timepoints for the determination of C24. Accumulation ratio of MK-1167 Day 31 to Day 1 was calculated as Day 31 C24/Day 1 C24.

Time frame: Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose