A Randomized Clinical Trial To Evaluate the Single Dose Acute Effects of MK-0249 and Donepezil On Cognitive Function In Adult Patients With Alzheimer's Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 4
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 65 Years to — (Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
PBO→MK-7.5→DON→MK-25
Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
PBO→MK-7.5→DON→MK-25
Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
PBO→MK-7.5→DON→MK-25
Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
PBO→MK-7.5→DON→MK-25
Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
PBO→MK-7.5→DON→MK-25
Treatment by single oral dose with Placebo (PBO) in the first crossover period; MK-0249 7.5 mg (MK-7.5) in the second crossover period; Donepezil 5 mg (DON) in the third crossover period; and MK-0249 25 mg (MK-25) in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-7.5→PBO→MK-25→DON
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
MK-7.5→PBO→MK-25→DON
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-7.5→PBO→MK-25→DON
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-7.5→PBO→MK-25→DON
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-7.5→PBO→MK-25→DON
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 25 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
DON→MK-25→PBO→MK-7.5
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
DON→MK-25→PBO→MK-7.5
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
DON→MK-25→PBO→MK-7.5
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
DON→MK-25→PBO→MK-7.5
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
DON→MK-25→PBO→MK-7.5
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-25→DON→MK-7.5→PBO
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
MK-25→DON→MK-7.5→PBO
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-25→DON→MK-7.5→PBO
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-25→DON→MK-7.5→PBO
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-25→DON→MK-7.5→PBO
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
PBO→MK-25→MK-7.5→DON
Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
PBO→MK-25→MK-7.5→DON
Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
PBO→MK-25→MK-7.5→DON
Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
PBO→MK-25→MK-7.5→DON
Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
PBO→MK-25→MK-7.5→DON
Treatment by single oral dose with Placebo in the first crossover period; MK-0249 25 mg in the second crossover period; MK-0249 7.5 mg in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-7.5→DON→PBO→MK-25
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
MK-7.5→DON→PBO→MK-25
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-7.5→DON→PBO→MK-25
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-7.5→DON→PBO→MK-25
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-7.5→DON→PBO→MK-25
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; Donepezil 5 mg in the second crossover period; Placebo in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
DON→MK-7.5→MK-25→PBO
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
DON→MK-7.5→MK-25→PBO
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
DON→MK-7.5→MK-25→PBO
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
DON→MK-7.5→MK-25→PBO
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
DON→MK-7.5→MK-25→PBO
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-25→PBO→DON→MK-7.5
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
PBO→DON→MK-25→MK-7.5
Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-25→PBO→DON→MK-7.5
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-25→PBO→DON→MK-7.5
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-25→PBO→DON→MK-7.5
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-25→PBO→DON→MK-7.5
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; Placebo in the second crossover period; Donepezil 5 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
PBO→DON→MK-25→MK-7.5
Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
PBO→DON→MK-25→MK-7.5
Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
PBO→DON→MK-25→MK-7.5
Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
PBO→DON→MK-25→MK-7.5
Treatment by single oral dose with Placebo in the first crossover period; Donepezil 5 mg in the second crossover period; MK-0249 25 mg in the third crossover period; and MK-0249 7.5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-7.5→MK-25→DON→PBO
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
MK-7.5→MK-25→DON→PBO
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-7.5→MK-25→DON→PBO
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-7.5→MK-25→DON→PBO
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-7.5→MK-25→DON→PBO
Treatment by single oral dose with MK-0249 7.5 mg in the first crossover period; MK-0249 25 mg in the second crossover period; Donepezil 5 mg in the third crossover period; and Placebo in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
DON→PBO→MK-7.5→MK-25
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
DON→PBO→MK-7.5→MK-25
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
DON→PBO→MK-7.5→MK-25
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
DON→PBO→MK-7.5→MK-25
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
DON→PBO→MK-7.5→MK-25
Treatment by single oral dose with Donepezil 5 mg in the first crossover period; Placebo in the second crossover period; MK-0249 7.5 mg in the third crossover period; and MK-0249 25 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
MK-25→MK-7.5→PBO→DON
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 7.5 mg (Drug)
MK-25→MK-7.5→PBO→DON
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: MK-0249 25 mg (Drug)
MK-25→MK-7.5→PBO→DON
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Donepezil 5mg (Drug)
MK-25→MK-7.5→PBO→DON
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to MK-0249 (Drug)
MK-25→MK-7.5→PBO→DON
Treatment by single oral dose with MK-0249 25 mg in the first crossover period; MK-0249 7.5 mg in the second crossover period; Placebo in the third crossover period; and Donepezil 5 mg in the fourth crossover period.
Intervention: Placebo to Donepezil (Drug)
Outcomes
Primary Outcomes
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
Time Frame: 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 Participants With Alzheimer's Disease
Time Frame: 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 Outcomes
- 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)
- 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)