A Phase 1 interventional study of Donepezil and Placebo in Alzheimer's Disease and Mild Cognitive Impairment, sponsored by Merck Sharp & Dohme LLC. Completed at 10 sites in 2 countries. Open to participants aged 55 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-10-28.
Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment
The main purpose of this study is to assess the ability of a repeated high-frequency site-based computerized cognitive assessment to evaluate the potential treatment effects of donepezil (MK-0000) compared with placebo among participants with mild cognitive impairment (MCI) or mild Alzheimer's Disease (AD). The primary study hypothesis is that the average percentage of correct responses on one card learning (OCL) task will be ≥2 percentage points in participants receiving donepezil compared with participants receiving placebo.
3,678 studies on the registry are indexed under Alzheimer Disease; 872 are open to participants now.
This study's enrollment of 44 is below the median of 70 across 2,808 interventional studies indexed under Alzheimer Disease.
Browse Alzheimer Disease studies →Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.
Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.
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Exclusion Criteria:
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.
Drug: Donepezil
Participants receive placebo QD, orally for Days 1-56. The total treatment duration is 56 Days.
Drug: Placebo
Donepezil 5 mg capsules for a total daily dose of up to 10 mg QD, orally, for Days 1-56.
Also known as: MK-0000, Donepezil hydrochloride, Aricept
Dose matched placebo capsule QD, orally for Days 1-56.
Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8
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.
Time frame: Baseline, Up to Week 8
Change From Baseline in Standard Deviation for Averaged Correct Response Rate on the OCL Task (Arcsine Square Root Transformed) to Week 8
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.
Time frame: Baseline, Up to Week 8
Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil
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.
Time frame: Baseline, Up to Week 8
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.
| Milestone | Donepezil | Placebo |
|---|---|---|
| Started | 29 | 15 |
| Completed | 28 | 14 |
| Not completed | 1 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 0 | 1 |
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.
| Proportion of correct response | Donepezil | Placebo |
|---|---|---|
| Change From Baseline in Averaged Correct Response Rate on the One Card Learning Task to Week 8 | 0.055 ± 0.078 | 0.034 ± 0.091 |
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.
| Arcsine sqrt transformed proportion CR | Donepezil | Placebo |
|---|---|---|
| MCI | 0.078 | 0.074 |
| Mild AD | 0.080 | 0.097 |
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.
| Proportion of correct response | Donepezil | Placebo |
|---|---|---|
| Change From Baseline in Averaged Correct Response Rate on the OCL Task to Week 8 in Participants Receiving Donepezil | 0.055 ± 0.078 | — |
Collected over Up to Week 10 (up to 70 days). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Donepezil | 0/29 (0%) | 1/29 (3.4%) | 16/29 (55.2%) |
| Placebo | 0/15 (0%) | 0/15 (0%) | 4/15 (26.7%) |
| Event | Donepezil | Placebo |
|---|---|---|
| PresyncopeNervous system disorders | 1/29 | 0/15 |
| Event | Donepezil | Placebo |
|---|---|---|
| DyspepsiaGastrointestinal disorders | 0/29 | 2/15 |
| Upper respiratory tract infectionInfections and infestations | 3/29 | 0/15 |
| Muscle spasmsMusculoskeletal and connective tissue disorders | 3/29 | 0/15 |
| Abnormal dreamsPsychiatric disorders | 3/29 | 0/15 |
| FatigueGeneral disorders | 2/29 | 1/15 |
| Urinary tract infectionInfections and infestations | 2/29 | 0/15 |
| HeadacheNervous system disorders | 2/29 | 1/15 |
| Otitis mediaInfections and infestations | 0/29 | 1/15 |
| DizzinessNervous system disorders | 0/29 | 1/15 |
| PruritusSkin and subcutaneous tissue disorders | 0/29 | 1/15 |
| Age, Continuous(Years) | Donepezil | Placebo | Total |
|---|---|---|---|
| Mean | 68.3 ± 7.6 | 68.4 ± 7.7 | 68.4 ± 7.5 |
| Sex: Female, Male(Participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| Female | 17 | 12 | 29 |
| Male | 12 | 3 | 15 |
| Ethnicity (NIH/OMB)(Participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| Hispanic or Latino | 12 | 7 | 19 |
| Not Hispanic or Latino | 17 | 8 | 25 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Donepezil | Placebo | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 1 | 0 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 9 | 6 | 15 |
| White | 19 | 9 | 28 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
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Merck Sharp & Dohme LLC