Alzheimer's Disease
Conditions
Brief summary
This study aims to determine whether the Cogstate testing battery can detect improvements in cognitive function in participants with mild AD. The primary hypothesis is that for one of the Cogstate battery tests, One Card Learning (OCL), the standard deviation associated with the change from baseline in OCL measurements after 12 weeks of donepezil and placebo treatments is =\<0.1
Interventions
DRUGPlacebo
Placebo for donepezil hydrochloride capsule
DRUGDonepezil
5 mg donepezil hydrochloride capsule.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Meets listed criteria for a diagnosis of probable AD * Has a clearly documented history either in medical records or from an informant of cognitive decline over at least 6 months * Has a reliable partner/caregiver who is willing to provide input by participating in assessments * Has results of a physical examination and clinical laboratory tests within normal or clinically acceptable limits * Can communicate with trial staff acceptably, possesses the ability to respond verbally to questions, follow instructions, complete questionnaires, and adhere to visit schedules * Can read at a 9th grade level or equivalent, and has an acceptable history of academic achievement and/or employment * Has a magnetic resonance imaging (MRI) scan that rules out non-AD conditions contributing to cognitive dysfunction * Capably performs the CogState screening battery * Has adequate visual acuity and function * Females are not of childbearing potential
Exclusion criteria
* Has ever received acetylcholinesterase inhibitors, memantine, or other symptomatic AD treatment including approved medical foods * Has an uncontrolled, clinically significant medical condition or situation within 3 months prior to screening * Has had major surgery within 3 months prior to screening * Has tested positive for human immunodeficiency virus (HIV) or has evidence of an active hepatitis B infection * Has a history of malignancy within the prior 5 years * Is unwilling or ineligible to undergo an MRI scan * Has a history of clinically important structural changes on screening MRI scan * Has a clinically important history of stroke or a diagnosis of vascular dementia * Has evidence of a clinically relevant non-AD neurological disorder * Has a history of head trauma, or serious infectious disease affecting the brain within the prior 3-5 years * Has evidence of a clinically relevant or unstable psychiatric disorder, excepting major depression in remission * Has evidence of a current episode of major depression * Has evidence of Type 4 or Type 5 Suicidal Ideation * Has clinically significant vitamin B12 or folate deficiency in the 6 months prior to screening * Is pregnant, attempting to become pregnant or is nursing children * Has used any investigational drug or participated in any other clinical trial within the prior 30 days * Has a history of alcoholism or drug dependency/abuse within the last 5 years * Has a relative contraindication to donepezil including sick sinus syndrome, third degree heart block, active gastrointestinal (GI) bleeding, Zollinger-Ellison syndrome, uncontrolled peptic ulcer disease, or uncontrolled asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Weeks 4, 8, 12 and 16 | OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. OCL is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCL questions. The score ranges from 0 to 1.5708 where a higher score means better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Weeks 4, 8, 12 and 16 | OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. The percentage of correct responses to 80 OCL questions is defined as the number of correct responses x 100 divided by the number of total responses; and ranges from 0 to 100, where 100 is best, and 0 is the worst outcome. |
Participant flow
Recruitment details
Males and females with mild Alzheimer's Disease (AD) between the ages of 55 and 85 years (inclusive) were enrolled in this trial.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo for donepezil hydrochloride capsule administered orally once a day for 16 weeks. | 6 |
| Donepezil During the first 4 weeks, participants received placebo for donepezil. Over the following 2 weeks, participants were treated with donepezil at 5 mg per day. Then, over the remaining 10 weeks were titrated to up to 10 mg per day donepezil based on tolerability. | 30 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Technical Problems | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo | Donepezil | Total |
|---|---|---|---|
| Age, Continuous | 76.7 Years STANDARD_DEVIATION 8.6 | 72.7 Years STANDARD_DEVIATION 8.7 | 73.4 Years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 2 Participants | 15 Participants | 17 Participants |
| Sex: Female, Male Male | 4 Participants | 15 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 9 / 28 |
| serious Total, serious adverse events | 0 / 6 | 1 / 28 |
Outcome results
Primary
One-card Learning (OCL) Measurement Over 12 Weeks of Treatment
OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. OCL is a score defined as the arcsine transformation of the square root of the proportion of correct responses to 80 OCL questions. The score ranges from 0 to 1.5708 where a higher score means better performance.
Time frame: Weeks 4, 8, 12 and 16
Population: All participants who received study medication and yielded at least one measurement for that endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 4 (n = 5, 28) | 0.954 Score on a scale | Standard Deviation 0.091 |
| Placebo | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 8 (n = 5, 22) | 0.822 Score on a scale | Standard Deviation 0.179 |
| Placebo | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 12 (n = 5, 21) | 0.849 Score on a scale | Standard Deviation 0.132 |
| Placebo | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 16 (n = 5, 21) | 0.961 Score on a scale | Standard Deviation 0.123 |
| Donepezil | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 16 (n = 5, 21) | 0.993 Score on a scale | Standard Deviation 0.112 |
| Donepezil | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 4 (n = 5, 28) | 0.942 Score on a scale | Standard Deviation 0.112 |
| Donepezil | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 12 (n = 5, 21) | 0.984 Score on a scale | Standard Deviation 0.118 |
| Donepezil | One-card Learning (OCL) Measurement Over 12 Weeks of Treatment | Week 8 (n = 5, 22) | 0.969 Score on a scale | Standard Deviation 0.104 |
Comparison: Change from Week 4 to Week 16 in Standard Deviation (SD) of OCL for Placebo + Donezepil treatment groups combined95% CI: [-0.031, 0.039]
Secondary
Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment
OCL is one of the Cogstate battery of tests, and is a continuous visual recognition task that assesses visual recognition, memory and attention using a pattern separation algorithm. The percentage of correct responses to 80 OCL questions is defined as the number of correct responses x 100 divided by the number of total responses; and ranges from 0 to 100, where 100 is best, and 0 is the worst outcome.
Time frame: Weeks 4, 8, 12 and 16
Population: All participants who received study medication and yielded at least one measurement for that endpoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 4 (n = 5, 28) | 66.2 Percentage of Corrrect Responses | Standard Deviation 8.3 |
| Placebo | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 12 (n = 5, 21) | 56.1 Percentage of Corrrect Responses | Standard Deviation 12.7 |
| Placebo | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 16 (n = 5, 21) | 66.7 Percentage of Corrrect Responses | Standard Deviation 11.6 |
| Placebo | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 8 (n = 5, 22) | 53.7 Percentage of Corrrect Responses | Standard Deviation 17.1 |
| Donepezil | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 8 (n = 5, 22) | 67.4 Percentage of Corrrect Responses | Standard Deviation 9.5 |
| Donepezil | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 4 (n = 5, 28) | 64.9 Percentage of Corrrect Responses | Standard Deviation 10.3 |
| Donepezil | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 16 (n = 5, 21) | 69.5 Percentage of Corrrect Responses | Standard Deviation 9.8 |
| Donepezil | Percentage of Correct Responses in the OCL Task Over 12 Weeks of Treatment | Week 12 (n = 5, 21) | 68.6 Percentage of Corrrect Responses | Standard Deviation 10.4 |