Trial Outcomes & Findings for Cognition Platform Study in Participants at Risk for Alzheimer's Disease (AD) (MK-0000-413) (NCT NCT04730635)

Last Updated: 2024-10-28

Results Overview

One Card Learning (OCL) uses a pattern separation paradigm to assess visual memory. The change from baseline of correct responses on the OCL task up to Week 8 is compared in participants receiving donepezil with participants receiving placebo. Change from baseline was the averaged correct response rate at Week 8 minus the correct response rate at baseline.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

44 participants

Primary outcome timeframe

Baseline, Up to Week 8

Results posted on

2024-10-28

Participant Flow

Treatment-naïve male and female participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) between the ages of 55 and 85 years (inclusive) will be enrolled in this trial.

Participant milestones

Participant milestones
Measure	Donepezil Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Overall Study STARTED	29	15
Overall Study COMPLETED	28	14
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Cognition Platform Study in Participants at Risk for Alzheimer's Disease (AD) (MK-0000-413)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil n=29 Participants Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo n=15 Participants Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.	Total n=44 Participants Total of all reporting groups
Age, Continuous	68.3 Years STANDARD_DEVIATION 7.6 • n=5 Participants	68.4 Years STANDARD_DEVIATION 7.7 • n=7 Participants	68.4 Years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	12 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	3 Participants n=7 Participants	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	17 Participants n=5 Participants	8 Participants n=7 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 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
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants	9 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Up to Week 8

Population: All participants who received at least one dose of study medication and yielded at least one measurement for that outcome measure.

Outcome measures

Outcome measures
Measure	Donepezil n=23 Participants Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo n=13 Participants Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8	0.055 Proportion of correct response Standard Deviation 0.078	0.034 Proportion of correct response Standard Deviation 0.091

SECONDARY outcome

Timeframe: Baseline, Up to Week 8

Population: All participants who received at least one dose of study medication and yielded at least one measurement for that outcome measure.

OCL uses a pattern separation paradigm to assess visual memory. Change in standard deviation from baseline for correct response rate on the OCL task up to Week 8 is compared in participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD) receiving donepezil with participants receiving placebo. Change from baseline was the standard deviation for correct response rate at Week 8 minus the standard deviation for correct response rate at baseline. Standard deviations are reported in arcsine square root (sqrt) transformed correct response (CR) rate.

Outcome measures

Outcome measures
Measure	Donepezil n=23 Participants Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo n=13 Participants Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8 MCI	0.078 Arcsine sqrt transformed proportion CR	0.074 Arcsine sqrt transformed proportion CR
Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8 Mild AD	0.080 Arcsine sqrt transformed proportion CR	0.097 Arcsine sqrt transformed proportion CR

SECONDARY outcome

Timeframe: Baseline, Up to Week 8

Population: All participants who received at least one dose of donepezil and yielded at least one measurement for that outcome measure. Per protocol, the placebo group was not included in this analysis.

OCL uses a pattern separation paradigm to assess visual memory. The change from baseline of correct responses on the OCL task up to Week 8 in participants receiving donepezil is presented. Change from baseline was the averaged correct response rate at Week 8 minus the correct response rate at baseline. Per protocol, the placebo group was not included in this analysis.

Outcome measures

Outcome measures
Measure	Donepezil n=23 Participants Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil	0.055 Proportion of correct response Standard Deviation 0.078	—

Adverse Events

Donepezil

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Donepezil n=29 participants at risk Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo n=15 participants at risk Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Nervous system disorders Presyncope	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.

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 The investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER

Measure	Donepezil n=29 participants at risk Participants receive donepezil in doses up to 10 mg once daily (QD), orally in a scheduled titration for Days 1-56. The total treatment duration is 56 days.	Placebo n=15 participants at risk Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Skin and subcutaneous tissue disorders Rash	0.00% 0/29 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Blood and lymphatic system disorders Anaemia	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Eye disorders Vitreous floaters	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/29 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	13.3% 2/15 • Number of events 2 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Nausea	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Gastrointestinal disorders Vomiting	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
General disorders Fatigue	6.9% 2/29 • Number of events 2 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Immune system disorders Food allergy	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Infections and infestations Otitis media	0.00% 0/29 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	10.3% 3/29 • Number of events 4 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Infections and infestations Urinary tract infection	6.9% 2/29 • Number of events 3 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Fall	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Injury, poisoning and procedural complications Skin laceration	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Investigations SARS-CoV-2 test positive	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	10.3% 3/29 • Number of events 3 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Dizziness	0.00% 0/29 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Headache	6.9% 2/29 • Number of events 2 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Nervous system disorders Radiculopathy	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Abnormal dreams	10.3% 3/29 • Number of events 3 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Emotional distress	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Hypnagogic hallucination	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Insomnia	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Psychiatric disorders Nightmare	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Renal and urinary disorders Micturition urgency	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/29 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	6.7% 1/15 • Number of events 2 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Pruritus allergic	3.4% 1/29 • Number of events 1 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.	0.00% 0/15 • Up to Week 10 (up to 70 days) All-Cause Mortality (ACM) was reported for all randomized participants. Serious AEs and Other AEs were reported for the Safety Population: all randomized participants who received at least 1 dose of study medication.