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)

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Alzheimer's Disease; Dementia

Treatments: Drug: MK-0249 7.5 mg; Drug: MK-0249 25 mg; Drug: Placebo to Donepezil; Drug: Donepezil 5mg; Drug: Placebo to MK-0249

Study type: Interventional

Funder types: Industry

Identifiers

NCT00874939

2009_572

MK-0249-023 (Other Identifier)

0249-023

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 65+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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4 participants in 12 patient groups

PBO→MK-7.5→DON→MK-25

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-7.5→PBO→MK-25→DON

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

DON→MK-25→PBO→MK-7.5

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-25→DON→MK-7.5→PBO

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

PBO→MK-25→MK-7.5→DON

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-7.5→DON→PBO→MK-25

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

DON→MK-7.5→MK-25→PBO

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-25→PBO→DON→MK-7.5

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

PBO→DON→MK-25→MK-7.5

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-7.5→MK-25→DON→PBO

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

DON→PBO→MK-7.5→MK-25

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg

MK-25→MK-7.5→PBO→DON

Experimental group

Description:

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.

Treatment:

Drug: MK-0249 25 mg

Drug: Placebo to Donepezil

Drug: Placebo to MK-0249

Drug: Donepezil 5mg

Drug: MK-0249 7.5 mg