Alzheimer's Disease, Dementia
Conditions
Brief summary
This study will evaluate acute symptomatic improvements in cognitive performance in healthy elderly participants with mild-to-moderate Alzheimer's disease. A four-week pilot study will first evaluate the CogState computerized cognitive battery in participants who are not receiving treatment. After completion of the pilot study, participants will be randomized to receive Placebo, Donepezil 5 mg, MK-0249 7.5 mg, and MK-0249 25 mg. After each drug administration the participants will be given the CogState computerized cognitive battery to assess cognitive performance. The primary hypotheses are that cognitive performance in participants with Alzheimer's disease, or in healthy participants, is improved by the administration of a single oral 5 mg dose of Donepezil as compared to placebo.
Interventions
DRUGMK-0249 7.5 mg
4 tablets (1 x 0.5 mg + 2 x 1 mg + 1 x 5 mg) totaling 7.5 mg, single oral dose during each crossover period
DRUGMK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
DRUGDonepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
DRUGPlacebo to MK-0249
Five tablets, single oral dose during each crossover period
DRUGPlacebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patient Specific: * Female is not of reproductive potential * Male who has a female partner(s) of child bearing potential, agrees to use acceptable method of contraception during the study * Has at least 10 years of education or work history * Has been a nonsmoker or has not used nicotine for at least 6 months * Has a diagnosis of mild-to-moderate Alzheimer's Disease * Has a reliable caregiver who consents to accompany the patient to all clinic visits, provide information to the study staff, and return for follow-up visits and procedures Healthy Elderly Volunteer Specific: * Is in good general health * Has no clinically significant abnormality on electrocardiogram (ECG)
Exclusion criteria
Participant Specific: * Has a history of a neurological disorder other than Alzheimer's disease * Is living in a nursing home * Has a history of stroke * Has a history of psychotic disorder, an active major depressive disorder, or history of schizophrenia * Has a history of a sleep disorder * Has a history of a cardiovascular disorder * Has a history of malignancy * Is participating or has participated in a study with an investigational compound, device, or vaccine for Alzheimer's disease * Consumes greater than 6 servings of caffeine (coffee, tea or cola etc.) per day * Consumes greater than 3 alcoholic beverages per day * Has had major surgery, donated or loss blood in past 8 weeks Healthy Elderly Volunteer Specific: * Is mentally or legally incapacitated, has significant emotional problems, or has a history of a psychiatric disorder over the last 5-10 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Participants With Alzheimer's Disease | Baseline and 5-7 hours post-dose | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. |
| Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Healthy Participants | Baseline and 5-7 hours post-dose | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Participants With Alzheimer's Disease. | Baseline and 5-7 hours post-dose | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. |
| Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Healthy Participants. | Baseline and 5-7 hours post-dose | The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function. |
Participant flow
Recruitment details
Eight participants were screened and four were enrolled in the study.
Pre-assignment details
The study was terminated prior to randomization and treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All enrolled participants | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study terminated | 4 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 67 Years STANDARD_DEVIATION 2.2 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Healthy Participants
The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function.
Time frame: Baseline and 5-7 hours post-dose
Population: Analysis was not performed due to termination of the study prior to randomization and treatment.
Primary
Time Weighted Average of the Change From Baseline After Single Dose Administration of Donepezil 5 mg or Placebo, Measured by Groton Maze Learning Test (GMLT) in Participants With Alzheimer's Disease
The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function.
Time frame: Baseline and 5-7 hours post-dose
Population: Analysis was not performed due to termination of the study prior to randomization and treatment.
Secondary
Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Healthy Participants.
The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function.
Time frame: Baseline and 5-7 hours post-dose
Population: Analysis was not performed due to termination of the study prior to randomization and treatment.
Secondary
Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Participants With Alzheimer's Disease.
The GMLT measures executive function and spatial problem solving on a computer touch screen where participants learn a hidden pathway through a maze consisting of a 10 x 10 grid of tiles. The number of errors made for five consecutive trials at a single session is totaled, where lower number of errors indicates better performance. A change from baseline that is positive indicates improved function.
Time frame: Baseline and 5-7 hours post-dose
Population: Analysis was not performed due to termination of the study prior to randomization and treatment.