Rogers, Arkansas 72758

  • Alzheimer's Disease

Purpose:

The study will investigate the effects on safety and pharmacokinetics (PK) of MK-1942 and donepezil when co-administered to participants with Alzheimer's Disease with mild-to-moderate cognitive impairment stably treated with donepezil. The objectives of this study include determining if the combination of MK-1942 with donepezil increases the incidence or severity of adverse events (AEs) previously reported for these agents, or results in unanticipated AEs in the patient population targeted for MK-1942 treatment. In addition, any changes in the PK parameters of either MK-1942 or donepezil as a result of co-administration will be assessed.


Criteria:

Inclusion Criteria: - Body mass index (BMI) ≥18 and ≤35 kg/m^2, inclusive. - Is in good health based on medical history, physical examination, vital sign measures and electrocardiogram performed prior to randomization. - Have a negative urine drug screen prior to randomization. - Have a history of cognitive and functional decline with gradual onset and slow progression for at least one year before screening that is either corroborated or well-documented. - Be receiving donepezil (maximum dose: ≥10-mg, ≤15-mg) for symptomatic treatment of cognitive impairment associated with Alzheimer's dementia. The dose level must be stable for at least 1 month prior to screening. - Have a reliable and competent trial partner/caregiver who has a close relationship with the subject, has face-to-face contact at least three days a week for a minimum of six waking hours a week, and is willing to accompany the participant, if desired, to trial visits. The trial partner/caregiver should understand the nature of the trial and adhere to trial requirements (e.g., dosing, visit schedules, and nature and number of evaluations). - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Male participants must refrain from donating sperm PLUS agree to study guidelines regarding abstinent and/or contraception during the intervention period and for at least an additional 90 days (a spermatogenesis cycle) after the last dose of study intervention: - A female participant is eligible to participate if she is a women of nonchildbearing potential by study criteria. Exclusion Criteria: - Is positive for hepatitis B surface antigen, hepatitis C antibodies or human immunodeficiency virus (HIV). - Is at imminent risk of self-harm, based on clinical interview and responses on the Columbia-Suicide Severity Rating Scale (CSSRS), or of harm to others in the opinion of the investigator. - Had major surgery, donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pretrial (screening) visit. - Has a history of uncontrolled, clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, renal, respiratory, genitourinary, or major neurological (including stroke and chronic seizures) abnormalities or diseases. - Candidates should not have a history of asthma, chronic obstructive pulmonary disease, urinary obstructions or gastrointestinal bleeding. - Has a history of cancer (malignancy) exceptions for (1) Adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or; (2) Other malignancies which have been successfully treated with appropriate follow up and therefore unlikely to recur for the duration of the study. - Has a history of significant multiple and/or severe allergies (e.g., food, drug, latex allergy), or has had an anaphylactic reaction or significant intolerability (i.e., systemic allergic reaction) to prescription or non-prescription drugs or food. - Has evidence of a clinically relevant or unstable psychiatric disorder, based on The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, including schizophrenia or other psychotic disorder, bipolar disorder, or delirium at the time of the pre-study (screening) visit, or has a history of clinically significant psychiatric disorder of the last 5 years. - Has participated in another investigational study within 4 weeks (or 5 half-lives, whichever is greater) prior to the pre-study (screening) visit.


Study is Available At:


Original ID:

1942-005


NCT ID:

NCT04308304


Secondary ID:

MK-1942-005


Study Acronym:

DDI


Brief Title:

MK-1942/Donepezil Interactions in Participants With Alzheimer's Disease (MK-1942-005)


Official Title:

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Pharmacokinetics of MK-1942 Administered to Alzheimer's Disease Patients Receiving Donepezil Treatment.


Overall Status:

Recruiting


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

50 Years


Maximum Age:

85 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Merck Sharp & Dohme Corp.


Oversight Authority:

There was an error processing this request


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

24


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Medical Director
Study Director
Merck Sharp & Dohme Corp.
Primary Contact:Toll Free Number
1-888-577-8839
Trialsites@merck.com

Study Dates

Start Date:February 16, 2021
Completion Date:September 20, 2021
Completion Type:Anticipated
Primary Completion Date:September 20, 2021
Primary Completion Type:Anticipated
Verification Date:February 2021
Last Changed Date:February 24, 2021
First Received Date:March 11, 2020

Study Outcomes

Outcome Type:Secondary Outcome
Measure:Time to Reach the Maximum Concentration in the Plasma after the Drug Dose (Tmax) of Donepezil
Time Frame:Days -1 and 28
Safety Issues:False
Description:Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Days -1 and 28 are intense PK sampling days. Samples to be taken pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose. On Day -1 time points are rela
Outcome Type:Secondary Outcome
Measure:Trough plasma concentration (Ctrough) of Donepezil
Time Frame:Days -1 and 28
Safety Issues:False
Description:Trough plasma concentration (Ctrough, measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Days -1 and 28 are intense PK sampling days. Samples to be taken pre-dose and 0.5, 1, 2, 3, 4, 6, 12
Outcome Type:Secondary Outcome
Measure:Maximum Amount of Drug in the Plasma (Cmax) of Donepezil
Time Frame:Days -1 and 28
Safety Issues:False
Description:Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Days -1 and 28; intense PK sampling days. Samples to be taken pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose. On Day -1 time points are relative to the morn
Outcome Type:Secondary Outcome
Measure:Amount of Drug in the Plasma from the Dose to Hour 24 (AUC0-24) of Donepezil
Time Frame:Days -1 and 28
Safety Issues:False
Description:AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Days -1 and 28 are intense PK sampling days. Samples to be taken pre-dose and 0.5, 1, 2, 3, 4, 6, 12 and 24 hours post-dose. On Day -1 time points are relative to the
Outcome Type:Secondary Outcome
Measure:The Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) was the apparent volume o
Outcome Type:Secondary Outcome
Measure:Apparent Clearance at Steady-state (CLss/F) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:The rate and extent of absorption of MK-1942 will be performed by assessment of the apparent plasma clearance following dosing (CLss/F). Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological process
Outcome Type:Secondary Outcome
Measure:Apparent Terminal t1/2 of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:Apparent Terminal T1/2 is the time required for a given drug concentration in the plasma to decrease by 50%. Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at 0.5, 1, 2, 3, 4, 6, and 12 hours post AM dose.
Outcome Type:Secondary Outcome
Measure:Time to Reach the Maximum Concentration in the Plasma after the Drug Dose (Tmax) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:Tmax is a measure of the time to reach the maximum concentration in the plasma after the drug dose. Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at 0.5, 1, 2, 3, 4, 6, and 12 hours post AM dose. On Day 2
Outcome Type:Secondary Outcome
Measure:Trough plasma concentration (Ctrough) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:Trough plasma concentration (Ctrough, measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at
Outcome Type:Secondary Outcome
Measure:Amount of Drug in the Plasma from the Dose to Hour 24 (AUC0-24) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:AUC0-24 is a measure of the total amount of drug in the plasma from the dose to Hour 24. Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at 0.5, 1, 2, 3, 4, 6, and 12 hours post AM dose. On Day 28 (or last
Outcome Type:Secondary Outcome
Measure:Amount of Drug in the Plasma from the Dose to Hour 12 (AUC0-12) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:AUC0-12 is a measure of the total amount of drug in the plasma from the dose to Hour 12. Samples for PK on Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at 0.5, 1, 2, 3, 4, 6, and 12 hours post AM dose. O
Outcome Type:Secondary Outcome
Measure:Maximum Amount of Drug in the Plasma (Cmax) of MK-1942
Time Frame:Days 1, 7, 14, 21, and 28
Safety Issues:False
Description:Cmax is a measure of the maximum amount of drug in the plasma after the dose is given. Days 1, 7, 14, 21, and 28 are intense PK sampling days. Blood samples will be taken predose, and at 0.5, 1, 2, 3, 4, 6, and 12 hours post AM dose. On Day 28 (or last da
Outcome Type:Primary Outcome
Measure:Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events
Time Frame:Up to Day 42
Safety Issues:False
Description:The number of participants with abnormal urinalysis results reported as adverse events will be presented.
Outcome Type:Primary Outcome
Measure:Number of Participants with Abnormal Clinical Hematology Test Results Reported as Adverse Events
Time Frame:Up to Day 42
Safety Issues:False
Description:The number of participants with abnormal clinical hematology results reported as adverse events will be presented.
Outcome Type:Primary Outcome
Measure:Number of Participants with Abnormal Clinical Chemistry Test Results Reported as Adverse Events
Time Frame:Up to Day 42
Safety Issues:False
Description:The number of participants with abnormal clinical chemistry results reported as adverse events will be presented.
Outcome Type:Primary Outcome
Measure:Percent Change from Baseline in Diastolic Blood Pressure at Day 42
Time Frame:Baseline and Day 42
Safety Issues:False
Description:Baseline will be Day 1. Change from Baseline will be calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Day 42 will be presented.
Outcome Type:Primary Outcome
Measure:Percent Change from Baseline in Systolic Blood Pressure at Day 42
Time Frame:Baseline and Day 42
Safety Issues:False
Description:Baseline will be Day 1. Change from Baseline will be calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Day 42 will be presented.
Outcome Type:Primary Outcome
Measure:Percent Change from Baseline in Heart Rate at Day 42
Time Frame:Baseline and Day 42
Safety Issues:False
Description:Baseline will be Day 1. Change from Baseline will be calculated by subtracting Baseline values from individual post-Baseline values. Mean change from Baseline up to Day 42 will be presented.
Outcome Type:Primary Outcome
Measure:Number of Participants Who Reported Suicidal Ideation and/or Behavior on Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame:From the first day of study treatment through study follow-up (Up to Day 42)
Safety Issues:False
Description:The number of participants with suicidality using the C-SSRS will be presented. The C-SSR will be used in this study only for the purpose of safety monitoring by measuring the incidence of different types of suicidality categories during treatment. C-SSRS
Outcome Type:Primary Outcome
Measure:Number of Participants with Abnormal (Impaired) Results on Targeted Neurological Exams
Time Frame:Baseline Up to Day 29
Safety Issues:False
Description:The number of participants with abnormal (impaired) results on targeted neurological exams will be presented. The targeted neurological exam contains Modules 1, 2 and 5 of the general examination, focusing on arousal, cranial nerve function, and gait and
Outcome Type:Primary Outcome
Measure:Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings
Time Frame:Baseline Up to Day 42
Safety Issues:False
Description:The number of participants with clinically significant 12-lead ECGs will be presented. Twelve lead ECGs will be obtained during the study using an ECG machine that automatically measured ECG parameters of PR, QRS, QT, and QT corrected by Bazett's formula
Outcome Type:Primary Outcome
Measure:Number of Participants Discontinuing Study Medication due to an Adverse Event
Time Frame:Up to Day 28 (last day of treatment)
Safety Issues:False
Description:The number of participants discontinuing study medication due to an AE will be presented. An AE is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment o
Outcome Type:Primary Outcome
Measure:Number of Participants Experiencing an Adverse Event (AE)
Time Frame:Up to Day 42 (post-study visit)
Safety Issues:False
Description:The number of participants experiencing an AE will be presented. An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedu

Study Interventions

Intervention Type:Drug
Name:Placebo
Description:Placebo to MK-1942, oral, capsule, all dosage levels, BID dosing for up to 28 days.
Arm Name:Placebo
Intervention Type:Drug
Name:Donepezil
Description:Donepezil, oral, 5-mg and/or 10-mg tablet (maximum dose 15 mg QD), QD dosing for up to 28 days
Arm Name:MK-1942
Intervention Type:Drug
Name:MK-1942
Description:MK-1942, oral, 1-mg, 5-mg and/or 10-mg capsules, BID dosing up to 28 days
Arm Name:MK-1942

Study Arms

Study Arm Type:Placebo Comparator
Arm Name:Placebo
Description:Placebo to MK-1942 BID x 21 [28] D All participants to receive Donepezil once daily.
Study Arm Type:Experimental
Arm Name:MK-1942
Description:Dose Level 1: 8-mg MK-1942 twice daily (BID) x 7 days (7D), Day 1 to Day 7; Dose Level 2: 15-mg MK-1942 BID x 7D, Day 8 to Day 14; Dose Level 3: 30-mg MK-1942 BID x 7D, Day 15 to Day 21; Dose Level 4: ≤50-mg MK-1942 BID x 7D (Provisional Dose Level), Day 22 to Day 28 All participants to receive Donepezil once daily.

Study Agencies

Agency Class:Industry
Agency Type:Lead Sponsor
Agency Name:Merck Sharp & Dohme Corp.

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: September 24, 2021

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