Phase 1
Completed N=27
MK-1942/Donepezil Interactions in Participants With Alzheimer's Disease (MK-1942-005)
Source: ClinicalTrials.gov NCT04308304 ↗Enrolled (actual)
27
Serious AEs
0.0%
Results posted
Aug 2024
Primary outcomePrimary: Number of Participants With ≥1 Adverse Event (AE) — 13; 4; 4; 5 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With ≥1 Adverse Event (AE) |
13; 4; 4; 5; 4 | — |
| PRIMARY Number of Participants Discontinuing From Study Therapy Due to an Adverse Event (AE) |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings |
1; 0; 0; 0; 1 | — |
| PRIMARY Number of Participants With Abnormal (Impaired) Results on Targeted Neurological Exams |
0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants Who Reported Suicidal Ideation and/or Behavior on Study Based on Responses to the Columbia Suicide Severity Rating Scale (C-SSRS) |
0; 0; 0; 0; 0 | — |
| PRIMARY Change From Baseline in Heart Rate (HR) |
-2.27; 2.56; 6.14; 0.21; -4.53 | — |
| PRIMARY Change From Baseline in Systolic Blood Pressure (SBP) |
2.48; -0.15; 0.88; 1.45; 5.93 | — |
| PRIMARY Mean Change From Baseline in Diastolic Blood Pressure (DBP) |
-0.95; 0.56; 1.17; 0.10; -1.73 | — |
| PRIMARY Number of Participants With Abnormal Clinical Chemistry Test Results Reported as Adverse Events |
1; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants With Abnormal Clinical Hematology Test Results Reported as Adverse Events |
0; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events |
10; 0; 0; 0; 0 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to 12 Hours Postdose (AUC0-12) of MK-1942 |
1760; 3580; 6650; 11600 | — |
| SECONDARY AUC From Dosing to 24 Hours Postdose (AUC0-24) of MK-1942 |
3530; 7160; 13330; 23200 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of MK-1942 |
239; 477; 876; 1360 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of MK-1942 |
101; 228; 386; 693 | — |
| SECONDARY Time to Reach Maximum Plasma Concentration (Tmax) of MK-1942 |
1.97; 1.98; 2.00; 2.00 | — |
| SECONDARY Apparent Terminal Plasma Half-Life (t½) of MK-1942 |
26.7 | — |
| SECONDARY Apparent Clearance at Steady-state (CLss/F) of MK-1942 |
11.7 | — |
| SECONDARY Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942 |
449 | — |
| SECONDARY AUC0-24 of Donepezil |
606; 919 | — |
| SECONDARY Cmax of Donepezil |
37.9; 53.3 | — |
| SECONDARY Ctrough of Donepezil |
20.1; 31.8 | — |
| SECONDARY Tmax of Donepezil |
2.05; 2.03 | — |
Eligibility 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.
Data sourced from ClinicalTrials.gov (NCT04308304). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.