DDI

CompletedPhase 1Results posted

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

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

Lead sponsor

Merck Sharp & Dohme LLC

Asset

MK-1942

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease

Key I/E criterion

•Study partner/caregiver required

Primary endpoints

•≥1 Adverse Event (AE)•Number of Participants Discontinuing From Study Therapy Due to an Adverse Event•Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID1942-005

Secondary IDMK-1942-005Merck Protocol Number

NCT IDNCT04308304

Timeline

Milestones

Study first posted2020-03-16actual

Study start2021-02-16actual

Primary completion2022-05-18actual

Study completion2022-05-18actual

Last update posted2024-08-15actual

Results first posted2024-08-15actual

Assets

Drug assets

MK-1942

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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.

Endpoints (46)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Safety / tolerability / PK

Other (unclassified)

Other clinical outcomes

Behavior / neuropsychiatric

2 endpoints

Primary/protocol endpoint

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:Up to 42 days

event count, event

Primary/registry result

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:Up to 42 days

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	0	-
MK-1942 15 mgn=19 Participants	0	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	0	-
Placebo ADn=5 Participants	0	-

Safety / tolerability / PK

28 endpoints

Primary/protocol endpoint

Number of Participants With ≥1 Adverse Event (AE)

Time frame:Up to Day 42

event count, event

Primary/protocol endpoint

Number of Participants Discontinuing From Study Therapy Due to an Adverse Event (AE)

Time frame:Up to Day 28

event count, event

Primary/protocol endpoint

Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings

Time frame:Up to Day 28

event count, event

Primary/protocol endpoint

Number of Participants With Abnormal Clinical Chemistry Test Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Primary/protocol endpoint

Number of Participants With Abnormal Clinical Hematology Test Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Primary/protocol endpoint

Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Primary/registry result

Number of Participants With ≥1 Adverse Event (AE)

Time frame:Up to Day 42

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mg + Donepezil ADn=22 Participants	13	-
MK-1942 15 mg + Donepezil ADn=19 Participants	4	-
MK-1942 30 mg + Donepezil ADn=15 Participants	4	-
MK-1942 50 mg + Donepezil ADn=15 Participants	5	-
Placebo + Donepezil ADn=5 Participants	4	-

Primary/registry result

Number of Participants Discontinuing From Study Therapy Due to an Adverse Event (AE)

Time frame:Up to Day 28

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mg ADn=22 Participants	0	-
MK-1942 15 mg ADn=19 Participants	0	-
MK-1942 30 mg ADn=15 Participants	0	-
MK-1942 50 mg ADn=15 Participants	0	-
Placebo ADn=5 Participants	0	-

Primary/registry result

Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECG) Findings

Time frame:Up to Day 28

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	1	-
MK-1942 15 mgn=19 Participants	0	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	0	-
Placebo ADn=5 Participants	1	-

Primary/registry result

Number of Participants With Abnormal Clinical Chemistry Test Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	1	-
MK-1942 15 mgn=19 Participants	0	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	1	-
Placebo ADn=5 Participants	0	-

Primary/registry result

Number of Participants With Abnormal Clinical Hematology Test Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	0	-
MK-1942 15 mgn=19 Participants	1	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	0	-
Placebo ADn=5 Participants	0	-

Primary/registry result

Number of Participants With Abnormal Urinalysis Results Reported as Adverse Events

Time frame:Up to 42 days

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	10	-
MK-1942 15 mgn=19 Participants	0	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	0	-
Placebo ADn=5 Participants	0	-

Secondary/protocol endpoint

Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to 12 Hours Postdose (AUC0-12) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

AUC From Dosing to 24 Hours Postdose (AUC0-24) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

Maximum Plasma Concentration (Cmax) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

Trough Plasma Concentration (Ctrough) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

Time to Reach Maximum Plasma Concentration (Tmax) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

time to event, event

Secondary/protocol endpoint

Apparent Terminal Plasma Half-Life (t½) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

Cmax of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/protocol endpoint

Tmax of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Secondary/registry result

Area Under the Plasma Concentration-Time Curve (AUC) From Dosing to 12 Hours Postdose (AUC0-12) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (least_squares_mean), hr*nmol/L	Reported bounds
MK-1942 8 mg + Donepezil ADn=18 Participants	1760	-1390 - 2240
MK-1942 15 mg + Donepezil ADn=17 Participants	3580	-2860 - 4490
MK-1942 30 mg + Donepezil ADn=15 Participants	6650	-5330 - 8280
MK-1942 50 mg + Donepezil ADn=15 Participants	11600	-9110 - 14700

Geometric Mean Ratio (GMR)0.6990% CI0.55 - 0.86

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.6695% CI0.53 - 0.82

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7495% CI0.55 - 1.00

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7795% CI0.56 - 1.05

'MK-1942 Alone PK' are unpublished data from MK-1942-004

Secondary/registry result

AUC From Dosing to 24 Hours Postdose (AUC0-24) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (least_squares_mean), hr*nmol/L	Reported bounds
MK-1942 8 mg + Donepezil ADn=18 Participants	3530	-2790 - 4470
MK-1942 15 mg + Donepezil ADn=17 Participants	7160	-5710 - 8970
MK-1942 30 mg + Donepezil ADn=15 Participants	13330	-10700 - 16600
MK-1942 50 mg + Donepezil ADn=15 Participants	23200	-18200 - 29500

Geometric Mean Ratio (GMR)0.6990% CI0.55 - 0.86

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.6695% CI0.53 - 0.82

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7495% CI0.55 - 1.00

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7795% CI0.56 - 1.05

'MK-1942 Alone PK' are unpublished data from MK-1942-004

Secondary/registry result

Maximum Plasma Concentration (Cmax) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (least_squares_mean), nmol/L	Reported bounds
MK-1942 8 mg + Donepezil ADn=18 Participants	239	-184 - 310
MK-1942 15 mg + Donepezil ADn=17 Participants	477	-371 - 613
MK-1942 30 mg + Donepezil ADn=15 Participants	876	-731 - 1050
MK-1942 50 mg + Donepezil ADn=15 Participants	1360	-1080 - 1720

Geometric Mean Ratio (GMR)0.6790% CI0.52 - 0.87

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.6895% CI0.52 - 0.87

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7995% CI0.59 - 1.06

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7495% CI0.51 - 1.08

'MK-1942 Alone PK' are unpublished data from MK-1942-004

Secondary/registry result

Trough Plasma Concentration (Ctrough) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (least_squares_mean), nmol/L	Reported bounds
MK-1942 8 mg + Donepezil ADn=18 Participants	101	-79.7 - 127
MK-1942 15 mg + Donepezil ADn=17 Participants	228	-188 - 277
MK-1942 30 mg + Donepezil ADn=15 Participants	386	-282 - 527
MK-1942 50 mg + Donepezil ADn=15 Participants	693	-528 - 910

Geometric Mean Ratio (GMR)0.6290% CI0.48 - 0.80

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.6795% CI0.55 - 0.81

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.6895% CI0.49 - 0.93

'MK-1942 Alone PK' are unpublished data from MK-1942-004

GMR0.7295% CI0.54 - 0.98

'MK-1942 Alone PK' are unpublished data from MK-1942-004

Secondary/registry result

Time to Reach Maximum Plasma Concentration (Tmax) of MK-1942

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

time to event, event

Posted result

Group	Value (median), Hours	Reported bounds
MK-1942 8 mg + Donepezil ADn=18 Participants	1.97	-0.93 - 3.00
MK-1942 15 mg + Donepezil ADn=17 Participants	1.98	-0.43 - 3.00
MK-1942 30 mg + Donepezil ADn=15 Participants	2.00	-1.00 - 5.95
MK-1942 50 mg + Donepezil ADn=15 Participants	2.00	-1.93 - 3.08

Secondary/registry result

Apparent Terminal Plasma Half-Life (t½) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (geometric_mean), Hours	Geometric coefficient of variation
MK-1942 50 mg + Donepezil ADn=15 Participants	26.7	27.7

Secondary/registry result

Cmax of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Geometric coefficient of variation
Donepezil Day -1n=20 Participants	37.9	56.4
Donepezil Day 28n=15 Participants	53.3	42.2

Geometric mean1.22

Secondary/registry result

Tmax of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

concentration, descriptive

Posted result

Group	Value (median), Hours	Reported bounds
Donepezil Day -1n=20 Participants	2.05	-0.00 - 4.00
Donepezil Day 28n=15 Participants	2.03	-1.00 - 3.95

Other clinical outcomes

4 endpoints

Primary/protocol endpoint

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Primary/protocol endpoint

Mean Change From Baseline in Diastolic Blood Pressure (DBP)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Primary/registry result

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Posted result

Group	Value (mean), mmHg	Standard error
MK-1942 8 mgn=22 Participants	2.48	2.08
MK-1942 15 mgn=19 Participants	-0.15	2.59
MK-1942 30 mgn=15 Participants	0.88	2.09
MK-1942 50 mgn=15 Participants	1.45	2.19
Placebo ADn=5 Participants	5.93	4.00

Primary/registry result

Mean Change From Baseline in Diastolic Blood Pressure (DBP)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Posted result

Group	Value (mean), mmHg	Standard error
MK-1942 8 mgn=22 Participants	-0.95	0.93
MK-1942 15 mgn=19 Participants	0.56	2.01
MK-1942 30 mgn=15 Participants	1.17	1.51
MK-1942 50 mgn=15 Participants	0.10	1.39
Placebo ADn=5 Participants	-1.73	3.36

Other (unclassified)

12 endpoints

Primary/protocol endpoint/low confidence

Number of Participants With Abnormal (Impaired) Results on Targeted Neurological Exams

Time frame:Up to 29 days

event count, event

Primary/protocol endpoint/low confidence

Change From Baseline in Heart Rate (HR)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Primary/registry result/low confidence

Number of Participants With Abnormal (Impaired) Results on Targeted Neurological Exams

Time frame:Up to 29 days

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
MK-1942 8 mgn=22 Participants	0	-
MK-1942 15 mgn=19 Participants	0	-
MK-1942 30 mgn=15 Participants	0	-
MK-1942 50 mgn=15 Participants	0	-
Placebo ADn=5 Participants	0	-

Primary/registry result/low confidence

Change From Baseline in Heart Rate (HR)

Time frame:Baseline (Day -1) and Days 1, 8, 15, and 22: 2 hours postdose

change from baseline, improvement

Posted result

Group	Value (mean), beats/min	Standard error
MK-1942 8 mgn=22 Participants	-2.27	1.25
MK-1942 15 mgn=19 Participants	2.56	1.65
MK-1942 30 mgn=15 Participants	6.14	2.27
MK-1942 50 mgn=15 Participants	0.21	2.81
Placebo ADn=5 Participants	-4.53	1.06

Secondary/protocol endpoint/low confidence

Apparent Clearance at Steady-state (CLss/F) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Secondary/protocol endpoint/low confidence

Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Secondary/protocol endpoint/low confidence

AUC0-24 of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Secondary/protocol endpoint/low confidence

Ctrough of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Secondary/registry result/low confidence

Apparent Clearance at Steady-state (CLss/F) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Posted result

Group	Value (geometric_mean), L/h	Geometric coefficient of variation
MK-1942 50 mg + Donepezil ADn=15 Participants	11.7	45.5

Secondary/registry result/low confidence

Apparent Volume of Distribution at Steady State (Vzss/F) of MK-1942

Time frame:Day 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Posted result

Group	Value (geometric_mean), Liters	Geometric coefficient of variation
MK-1942 50 mg + Donepezil ADn=15 Participants	449	41.1

Secondary/registry result/low confidence

AUC0-24 of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Posted result

Group	Value (geometric_mean), hr*ng/mL	Geometric coefficient of variation
Donepezil Day -1n=20 Participants	606	66.4
Donepezil Day 28n=15 Participants	919	44.4

Geometric mean1.34

Secondary/registry result/low confidence

Ctrough of Donepezil

Time frame:Days 1, 7, 14, and 21 (morning dose only): predose and 0.5, 1, 2, 3, 4, 6, and 12 hours postdose

descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Geometric coefficient of variation
Donepezil Day -1n=20 Participants	20.1	72.7
Donepezil Day 28n=15 Participants	31.8	52.5

Geometric mean1.46

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.