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)

NCT00874939 | Terminated Phase 1 Results

• 3 other identifiers: 0249-023MK-0249-0232009_572
• Study Type: interventional
• Target: 4
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Alzheimer's Disease; Dementia

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline and 5-7 hours post-dose

• 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.

  Baseline and 5-7 hours post-dose

Secondary Outcomes (2)

• 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

Study Arms (12)

PBO→MK-7.5→DON→MK-25

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-7.5→PBO→MK-25→DON

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

DON→MK-25→PBO→MK-7.5

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-25→DON→MK-7.5→PBO

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

PBO→MK-25→MK-7.5→DON

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-7.5→DON→PBO→MK-25

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

DON→MK-7.5→MK-25→PBO

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-25→PBO→DON→MK-7.5

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

PBO→DON→MK-25→MK-7.5

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-7.5→MK-25→DON→PBO

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

DON→PBO→MK-7.5→MK-25

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

MK-25→MK-7.5→PBO→DON

EXPERIMENTAL

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; Drug: MK-0249 25 mg; Drug: Donepezil 5mg; Drug: Placebo to MK-0249; Drug: Placebo to Donepezil

Interventions

MK-0249 7.5 mg DRUG

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

DON→MK-25→PBO→MK-7.5; DON→MK-7.5→MK-25→PBO; DON→PBO→MK-7.5→MK-25; MK-25→DON→MK-7.5→PBO; MK-25→MK-7.5→PBO→DON; MK-25→PBO→DON→MK-7.5; MK-7.5→DON→PBO→MK-25; MK-7.5→MK-25→DON→PBO; MK-7.5→PBO→MK-25→DON; PBO→DON→MK-25→MK-7.5; PBO→MK-25→MK-7.5→DON; PBO→MK-7.5→DON→MK-25

MK-0249 25 mg DRUG

5 x 5 mg tablets totaling 25 mg, single oral dose during each crossover period

DON→MK-25→PBO→MK-7.5; DON→MK-7.5→MK-25→PBO; DON→PBO→MK-7.5→MK-25; MK-25→DON→MK-7.5→PBO; MK-25→MK-7.5→PBO→DON; MK-25→PBO→DON→MK-7.5; MK-7.5→DON→PBO→MK-25; MK-7.5→MK-25→DON→PBO; MK-7.5→PBO→MK-25→DON; PBO→DON→MK-25→MK-7.5; PBO→MK-25→MK-7.5→DON; PBO→MK-7.5→DON→MK-25

Donepezil 5mg DRUG

One 5 mg tablet, single oral dose during each crossover period

Also known as: Aricept

DON→MK-25→PBO→MK-7.5; DON→MK-7.5→MK-25→PBO; DON→PBO→MK-7.5→MK-25; MK-25→DON→MK-7.5→PBO; MK-25→MK-7.5→PBO→DON; MK-25→PBO→DON→MK-7.5; MK-7.5→DON→PBO→MK-25; MK-7.5→MK-25→DON→PBO; MK-7.5→PBO→MK-25→DON; PBO→DON→MK-25→MK-7.5; PBO→MK-25→MK-7.5→DON; PBO→MK-7.5→DON→MK-25

Placebo to MK-0249 DRUG

Five tablets, single oral dose during each crossover period

DON→MK-25→PBO→MK-7.5; DON→MK-7.5→MK-25→PBO; DON→PBO→MK-7.5→MK-25; MK-25→DON→MK-7.5→PBO; MK-25→MK-7.5→PBO→DON; MK-25→PBO→DON→MK-7.5; MK-7.5→DON→PBO→MK-25; MK-7.5→MK-25→DON→PBO; MK-7.5→PBO→MK-25→DON; PBO→DON→MK-25→MK-7.5; PBO→MK-25→MK-7.5→DON; PBO→MK-7.5→DON→MK-25

Placebo to Donepezil DRUG

One over-encapsulated capsule, single oral dose during each crossover period

DON→MK-25→PBO→MK-7.5; DON→MK-7.5→MK-25→PBO; DON→PBO→MK-7.5→MK-25; MK-25→DON→MK-7.5→PBO; MK-25→MK-7.5→PBO→DON; MK-25→PBO→DON→MK-7.5; MK-7.5→DON→PBO→MK-25; MK-7.5→MK-25→DON→PBO; MK-7.5→PBO→MK-25→DON; PBO→DON→MK-25→MK-7.5; PBO→MK-25→MK-7.5→DON; PBO→MK-7.5→DON→MK-25

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

MK-0249; Donepezil

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2009
• First Posted: April 3, 2009
• Study Start: April 6, 2009
• Primary Completion: April 20, 2009
• Study Completion: April 20, 2009
• Last Updated: October 17, 2018
• Results First Posted: June 8, 2015

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share