A Study Versus E2020 10mg Followed by an Open-label Extension Phase to Explore the Safety of E2020 SR 23 mg in Japanese Subjects With Severe Alzheimer's Type Dementia

Study Overview
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Brief Summary
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The purpose of this study is to compare 23 mg donepezil sustained release (SR) to the currently marketed formulation of 10 mg donepezil immediate release (IR) in patients with severe Alzheimer's disease.

Official Title
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A Randomized, Double Blind, Parallel-Group Comparison Study Versus E2020 10mg Followed by an Open-label Extension Phase to Explore the Safety of E2020 SR 23 mg in Japanese Subjects With Severe Alzheimer's Type Dementia

Conditions
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Alzheimer's Type Dementia

Intervention / Treatment
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* Drug: E2020
* Drug: E2020


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Diagnostic evidence of probable Alzheimer's disease (AD) consistent with the Diagnostic and Statistical Manual for Mental Disorders-version IV (DSM-IV) Hachinski Ischemic Score Functional Assessment Staging (FAST) scale greater than or equal to 6 at Screening. Mini-Mental State Examination (MMSE) score of 1 to 12 at Screening Subjects who are on a stable Aricept- dose of 10 mg immediate release (IR), taken as a single, daily dose for 3 months prior to the Screening Visit Evidence consistent with Alzheimer's disease (AD) on any cranial image on magnetic resonance imaging (MRI) or computed tomography (CT) scan or etc. obtained within 24 months prior to the Screening Visit. Subjects who have any observations of dementia other than Alzheimer's type after the last image diagnosis should be reconfirmed. Age 50 years Written informed consent is to have been obtained from the subject (if possible) or from the subject's legal guardian or other representative Exclusion Criteria Subjects with dementia other than Alzheimer's type Subjects with significant neurological or psychiatric disorders such as stroke, brain tumor, schizophrenia, epilepsy, normal pressure hydrocephalus, mental retardation, a history of head injury with loss of consciousness, or a history of brain surgery followed by persistent deficits Subjects with allergy to donepezil hydrochloride or piperidine derivatives Subjects with a cause of Alzheimer's disease (AD) which is supported by any laboratory tests such as Vitamin B12, folate levels, triiodothyronine, free triiodothyronine, thyroxine, thyroid stimulating hormone (TSH) or serologic test for syphilis

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: E2020<br>* Patients will take study medication orally, once daily, for 2 weeks according to a double-dummy design in the double blind phase: 23 mg donepezil sustained release (SR) concurrently with placebo identical in appearance to the 10 mg donepezil immediate release (IR) formulation<br>|
| Active Comparator: 2<br> | Drug: E2020<br>* 10 mg donepezil immediate release (IR) concurrently with placebo identical in appearance to the 23 mg donepezil sustained release (SR) formulation. All patients who complete the double blind phase will take 23 mg donepezil sustained release (SR) orally, once daily, for 52 weeks in the Open-label Extension phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 |  | Visit 2 [Day1] and Visit 3 [Day 15] | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | All subjects were identified as Extensive Metabolizer [EM] or Intermediate Metabolizer [IM] predicted from their CYP2D6 phenotypes. Ultra-rapid Metabolizer (UM) and Poor Metabolizer (PM) were not identified in any subject. Since the analysis population i | Visit 2 [Day1] and Visit 3 [Day 15] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer Disease, Dementia, Delirium, Amnestic, Cognitive Disorders, Donepezil, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Mental Disorders, Cholinesterase Inhibitors, Enzy