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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Alzheimer's Disease

Treatments: Drug: Placebo; Drug: MK-1942; Drug: Donepezil

Study type: Interventional

Funder types: Industry

Identifiers

NCT04308304

MK-1942-005 (Other Identifier)

1942-005

Details and patient eligibility

About

The study investigated 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 were to determine if the combination of MK-1942 with donepezil increases the incidence or severity of adverse events (AEs) previously reported for these agents alone, or results in unanticipated AEs in the patient population targeted for MK-1942 treatment. In addition, changes in the PK parameters of either MK-1942 or donepezil as a result of co-administration were assessed.

Enrollment: 27 patients

Sex: All

Ages: 50 to 85 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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27 participants in 2 patient groups, including a placebo group

Donepezil

Experimental group

Description:

Participants receive 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.

Treatment:

Drug: Donepezil

Drug: MK-1942

Placebo

Placebo Comparator group

Description:

Placebo to MK-1942 BID x 21 \[28\] D All participants to receive Donepezil once daily.

Treatment:

Drug: Donepezil

Drug: Placebo