A 24-weeks, Multi-center, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Donepezil Hydrochloride in Chinese Subjects With Severe Alzheimer's Disease

Study Overview
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Brief Summary
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The objective is to demonstrate that donepezil hydrochloride 10 mg/day has superior efficacy compared with placebo in cognitive function in Chinese subjects with severe Alzheimer's Disease.

Official Title
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A 24-weeks, Multi-center, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Donepezil Hydrochloride in Chinese Subjects With Severe Alzheimer's Disease

Conditions
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Alzheimer's Type Dementia

Intervention / Treatment
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* Drug: E2020
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Written informed consent (IC) will be obtained from the subject (if possible) or from the subject's legal guardian or legal representative prior to beginning screening activities. Subject age range: male and female subjects 50 to 90 years of age, inclusive Diagnosis: diagnostic evidence of probable Alzheimer's Disease (AD) consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria MMSE 1 to 12 inclusive, at both Screening and Baseline SIB less than or equal to 90 and greater than or equal to 10 at both Screening and Baseline Comorbid medical conditions must be clinically stable prior to Baseline, unless otherwise specified. Exclusion Criteria Subjects with a known history of disorders that affect cognition or the ability to assess cognition, but are distinguishable from AD Evidence of focal disease to account for dementia on any cranial image MRI or CT. Subjects with dementia complicated by other organic disease or AD with delirium according to DSM-IV criteria Subjects who cannot swallow or who have difficulty swallowing whole tablets, as tablets should not be broken or crushed Illiteracy prior to AD Subjects who are unwilling or unable to fulfill the requirements of the study Treatment with another cholinesterase inhibitor and/or memantine in the 3 months prior to Screening Subjects with a poor response (tolerability) to prior exposure to donepezil

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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>* In titration period, donepezil 5-mg tablet will be taken orally once daily for 6 weeks, following donepezil 10 mg tablets taken orally once daily for 18 weeks in the maintenance period.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo matched to donepezil 5 mg or 10 mg tablets taken orally once daily for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the total Severe Impairment Battery (SIB) score at Week 24 | All statistical tests will be conducted at the 0.05 level of significance (two-tailed). A positive outcome will be declared if for the primary efficacy endpoint as measured by the Severe Impairment Battery (SIB), the change from Baseline to Week 24 in the total SIB score last observation carried forward (LOCF) demonstrates superiority for donepezil 10 mg, compared with placebo. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinician Interview-Based Impression of Severity (CIBIC)+ overall score at Week 24 | An ANCOVA with embedded Cochran-Mantel-Haenszel (CMH) test will be used with the CIBIC+ and center in the model. Overall change from Baseline in scores at Week 24 (LOCF) will be analyzed with the same model as the SIB. | 24 weeks | 

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