A Study to Evaluate the Effects of MK-0249 and an Alzheimer's Disease Medication on Cognitive Function in Adults With Alzheimer's Disease (MK-0249-023)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00874939
First received: April 2, 2009
Last updated: May 26, 2015
Last verified: May 2015
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Dementia
Drug: MK-0249 7.5 mg
Drug: MK-0249 25 mg
Drug: Donepezil 5mg
Drug: Placebo to MK-0249
Drug: Placebo to Donepezil
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and 5-7 hours post-dose ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Time Weighted Average of the Change From Baseline After Single Dose Administration of MK-0249, Measured by GMLT in Participants With Alzheimer's Disease. [ Time Frame: Baseline and 5-7 hours post-dose ] [ Designated as safety issue: No ]
    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. [ Time Frame: Baseline and 5-7 hours post-dose ] [ Designated as safety issue: No ]
    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.


Enrollment: 4
Study Start Date: April 2009
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period
Experimental: 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.
Drug: MK-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
Drug: MK-0249 25 mg
5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period
Drug: Donepezil 5mg
One 5 mg tablet, single oral dose during each crossover period
Other Name: Aricept
Drug: Placebo to MK-0249
Five tablets, single oral dose during each crossover period
Drug: Placebo to Donepezil
One over-encapsulated capsule, single oral dose during each crossover period

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874939

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00874939     History of Changes
Other Study ID Numbers: 0249-023, MK-0249-023, 2009_572
Study First Received: April 2, 2009
Results First Received: May 26, 2015
Last Updated: May 26, 2015
Health Authority: India: Ministry of Health

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Dementia
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies
Donepezil
Central Nervous System Agents
Cholinergic Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Nootropic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on September 02, 2015