Trial Outcomes & Findings for Efficacy and Safety of MK-1942 as an Adjunct Therapy in Participants With Mild to Moderate Alzheimer's Disease Dementia (MK-1942-008) (NCT NCT05602727)

Last Updated: 2024-12-10

Results Overview

The change from baseline in ADAS-Cog11 score is presented. ADAS-Cog11 is a structured scale that evaluates memory, orientation, attention, reasoning, language, and constructional praxis. ADAS-Cog11 measures cognition by assessing 11 metrics impaired in AD: word recall; commands; constructional praxis; naming objects and fingers; ideational praxis; orientation; word recognition; remembering test instructions; spoken language ability; word-finding difficulty; and comprehension of spoken language. The total possible score ranges from 0 to 70, with higher scores indicating greater cognitive impairment. Negative values indicate improvement relative to baseline, and vice versa.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

99 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2024-12-10

Participant Flow

Participants were enrolled at study sites located in USA, UK, Spain, Japan, Republic of Korea, Canada, Argentina, and Australia.

Participant milestones

Participant milestones
Measure	MK-1942 5 mg Participants received MK-1942 5 mg twice daily (BID) for 12 weeks without dose titration.	MK-1942 15 mg Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Overall Study STARTED	35	31	33
Overall Study COMPLETED	13	8	12
Overall Study NOT COMPLETED	22	23	21

Reasons for withdrawal

Reasons for withdrawal
Measure	MK-1942 5 mg Participants received MK-1942 5 mg twice daily (BID) for 12 weeks without dose titration.	MK-1942 15 mg Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Overall Study Physician Decision	0	1	0
Overall Study Randomized by mistake without study medication	1	0	0
Overall Study Study termination by Sponsor	18	15	19
Overall Study Withdrawal by Subject	2	1	1
Overall Study Various reasons	1	6	1

Baseline Characteristics

Efficacy and Safety of MK-1942 as an Adjunct Therapy in Participants With Mild to Moderate Alzheimer's Disease Dementia (MK-1942-008)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MK-1942 5 mg n=35 Participants Participants received MK-1942 5 mg twice daily (BID) for 12 weeks without dose titration.	MK-1942 15 mg n=31 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=33 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.	Total n=99 Participants Total of all reporting groups
Age, Continuous	74.1 Years STANDARD_DEVIATION 7.5 • n=5 Participants	74.7 Years STANDARD_DEVIATION 8.0 • n=7 Participants	72.3 Years STANDARD_DEVIATION 8.2 • n=5 Participants	73.7 Years STANDARD_DEVIATION 7.9 • n=4 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	21 Participants n=7 Participants	23 Participants n=5 Participants	69 Participants n=4 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants	25 Participants n=7 Participants	31 Participants n=5 Participants	89 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	28 Participants n=7 Participants	26 Participants n=5 Participants	83 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Randomized participants who received ≥1 dose of study treatment, and who have baseline and a post-baseline assessment available, are included. A mixed-model repeated measures analyses was used in which partial data from participants not completing the study was utilized.

Outcome measures

Outcome measures
Measure	MK-1942 5 mg n=20 Participants Participants received MK-1942 5 mg BID for 12 weeks without dose titration.	MK-1942 15 mg n=21 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=25 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Change From Baseline in the Alzheimer's Disease Assessment Scale-11-item Cognitive Subscale (ADAS-Cog11) Score at Week 12	2.9 Units on a scale Interval 0.7 to 5.1	-0.6 Units on a scale Interval -3.0 to 1.8	0.8 Units on a scale Interval -1.4 to 3.0

PRIMARY outcome

Timeframe: Up to ~ 14 Weeks

Population: All randomized participants who received ≥1 dose of study treatment are included.

An AE is 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.

Outcome measures

Outcome measures
Measure	MK-1942 5 mg n=34 Participants Participants received MK-1942 5 mg BID for 12 weeks without dose titration.	MK-1942 15 mg n=31 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=33 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Number of Participants Experiencing an Adverse Event (AE)	17 Participants	21 Participants	18 Participants

PRIMARY outcome

Timeframe: Up to ~ 12 Weeks

Population: All participants who received ≥1 dose of study treatment are included.

Outcome measures

Outcome measures
Measure	MK-1942 5 mg n=34 Participants Participants received MK-1942 5 mg BID for 12 weeks without dose titration.	MK-1942 15 mg n=31 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=33 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Number of Participants Discontinuing Study Medication Due to an Adverse Event	4 Participants	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 12

Population: Randomized participants who received ≥1 dose of study treatment, and who have the relevant assessment available, are included.

The overall score in ADCS-CGIC is presented. ADCS-CGIC is a global scale assessing cognition and function based on structured interviews of both the participant and study partner. ADCS-CGIC focuses on clinicians' observations of change in the patient's cognitive, functional, and behavioral performance since the beginning of the study. Improvement in the ADCS-CGIC overall score, with a score of 1, 2, or 3 indicates improvement. The ADCS-CGIC is a clinician-rated measure of global severity at baseline scored from 1 (normal, not at all ill) to 7 (among the most extremely ill patients); and global change at follow-up scored from 1 (marked improvement) to 7 (marked worsening), where 4 indicates no change.

Outcome measures

Outcome measures
Measure	MK-1942 5 mg n=14 Participants Participants received MK-1942 5 mg BID for 12 weeks without dose titration.	MK-1942 15 mg n=11 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=13 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Alzheimer's Disease Cooperative Study Clinical Global Impression of Change (ADCS-CGIC) Overall Score at Week 12	5.4 Units on a scale Standard Deviation 0.7	5.8 Units on a scale Standard Deviation 0.9	5.3 Units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline and Week 12

The change from baseline in ADCS-ADL score is presented. The ADCS-ADL is an informant-based measure of the participant's functional ability in activities of daily living. The ADCS-ADL assesses the competence of participants with AD dementia in basic and instrumental ADLs. The ADCS-ADL is a 23-item scale that includes 6 basic ADL items and 17 instrumental ADL items that provide a total score ranging from 0 to 78, with a lower score indicating greater severity.

Outcome measures

Outcome measures
Measure	MK-1942 5 mg n=20 Participants Participants received MK-1942 5 mg BID for 12 weeks without dose titration.	MK-1942 15 mg n=21 Participants Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=25 Participants Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Mean Change From Baseline in The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Total Score at Week 12	-1.7 Units on a scale Interval -4.8 to 1.4	-3.0 Units on a scale Interval -6.4 to 0.4	1.2 Units on a scale Interval -2.0 to 4.4

Adverse Events

MK-1942 5 mg

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

MK-1942 15 mg

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MK-1942 5 mg n=34 participants at risk Participants received MK-1942 5 mg twice daily (BID) for 12 weeks without dose titration.	MK-1942 15 mg n=31 participants at risk Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=33 participants at risk Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Cardiac disorders Bradycardia	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
General disorders Asthenia	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
General disorders Chest pain	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.2% 1/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Injury, poisoning and procedural complications Fall	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.2% 1/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Nervous system disorders Hemiparesis	2.9% 1/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Nervous system disorders Syncope	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	MK-1942 5 mg n=34 participants at risk Participants received MK-1942 5 mg twice daily (BID) for 12 weeks without dose titration.	MK-1942 15 mg n=31 participants at risk Participants received MK-1942 8 mg BID for 1 week, followed by MK-1942 15 mg BID for the next 11 weeks.	Placebo n=33 participants at risk Participants received an inert placebo matched to MK-1942 BID for 12 weeks.
Gastrointestinal disorders Abdominal pain	5.9% 2/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.2% 1/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Gastrointestinal disorders Diarrhoea	8.8% 3/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Gastrointestinal disorders Nausea	2.9% 1/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	16.1% 5/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Gastrointestinal disorders Vomiting	2.9% 1/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	9.7% 3/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
General disorders Fatigue	2.9% 1/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.5% 2/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
General disorders Feeling abnormal	5.9% 2/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Infections and infestations COVID-19	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.1% 2/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.5% 2/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Injury, poisoning and procedural complications Fall	8.8% 3/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	12.1% 4/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Investigations Alanine aminotransferase increased	29.4% 10/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	16.1% 5/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Investigations Aspartate aminotransferase increased	2.9% 1/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.5% 2/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.1% 2/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Nervous system disorders Dizziness	11.8% 4/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	16.1% 5/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	12.1% 4/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Nervous system disorders Headache	8.8% 3/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.2% 1/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	3.0% 1/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.
Vascular disorders Hypertension	0.00% 0/34 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	6.5% 2/31 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.	0.00% 0/33 • Up to ~14 weeks All participants who received ≥1 dose of study treatment are included.