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
Overview
- Phase
- Phase 1
- Intervention
- MK-1167
- Conditions
- Alzheimer's Disease
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 28
- Locations
- 3
- Primary Endpoint
- Number of Participants Who Experienced an Adverse Event (AE)
- Status
- Completed
- Last Updated
- 6 months ago
Overview
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.
Investigators
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.
Arms & Interventions
Panel A: MK-1167 + Donepezil 10mg QD
Participants receive 6mg MK-1167 oral loading doses once daily (QD) Days 1 to 7, followed by 3mg MK-1167 oral maintenance doses QD Days 8 to 21. Participants also receive 10mg oral Donepezil on Days -3 to 21.
Intervention: MK-1167
Panel A: MK-1167 + Donepezil 10mg QD
Participants receive 6mg MK-1167 oral loading doses once daily (QD) Days 1 to 7, followed by 3mg MK-1167 oral maintenance doses QD Days 8 to 21. Participants also receive 10mg oral Donepezil on Days -3 to 21.
Intervention: Donepezil
Panel A: Placebo to MK-1167 + Donepezil 10mg QD
Participants receive dose matched placebo to MK-1167 oral QD from Days 1 to 21. Participants also receive 10mg oral Donepezil QD on Days -3 to 21.
Intervention: Donepezil
Panel A: Placebo to MK-1167 + Donepezil 10mg QD
Participants receive dose matched placebo to MK-1167 oral QD from Days 1 to 21. Participants also receive 10mg oral Donepezil QD on Days -3 to 21.
Intervention: Placebo
Panel B: MK-1167 6mg QD + Donepezil 10mg QD
Participants receive 6mg MK-1167 oral doses QD Days 1 to 31. Participants also receive 10mg oral Donepezil on Days -3 to 31.
Intervention: MK-1167
Panel B: MK-1167 6mg QD + Donepezil 10mg QD
Participants receive 6mg MK-1167 oral doses QD Days 1 to 31. Participants also receive 10mg oral Donepezil on Days -3 to 31.
Intervention: Donepezil
Panel B: Placebo to MK-1167 + Donepezil 10mg QD
Participants receive dose matched placebo to MK-1167 oral QD from Days 1 to 31. Participants also receive 10mg oral Donepezil QD on Days -3 to 31.
Intervention: Donepezil
Panel B: Placebo to MK-1167 + Donepezil 10mg QD
Participants receive dose matched placebo to MK-1167 oral QD from Days 1 to 31. Participants also receive 10mg oral Donepezil QD on Days -3 to 31.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants Who Experienced an Adverse Event (AE)
Time Frame: Up to approximately 7 weeks
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.
Number of Participants Who Discontinued Study Treatment Due to an AE
Time Frame: Up to approximately 4 weeks
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 discontinued study treatment due to an AE were reported.
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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(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(Days 1, 31: Predose and 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose)