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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

Primary Purpose

Alzheimer's Type Dementia

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
E2020
Placebo
Sponsored by
Eisai Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Type Dementia focused on measuring 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

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Beijing Anding Hospital
  • Beijing Hospital
  • Beijing Huilongguan Hospital
  • Chinese PLA General Hospital
  • Xuanwu Hospital Capital Medical University
  • The First Affiliated Hospital of Chongqing Medical University
  • The Second Affiliated Hospital of Chongqing Medical University
  • Guangzhou Brain Hospital
  • Guangzhou First People's Hospital
  • The People's Hospital of Guangxi Zhuang Autonomous Region
  • Tongji Hospital, Tongji Medical College of HUST
  • Union Hospital, Tongji Medical college Huazhong University of Science and Technology
  • The Third Xiangya Hospital of Central South University
  • The First People's Hospital of YueYang
  • Qilu Hospital of Shandong University
  • The Second Hospital of Shandong University
  • The Affiliated Hospital of Medical College Qingdao University
  • Hushan Hospital affliated to Fudan University
  • Renji Hospital, Shanghai Jiaotong University School of Medicine
  • Shanghai Changzheng Hospital
  • Shanghai Ruijin Hospital
  • Tangdu Hospital, The Fourth Military Medical University
  • Xi'An Mental Health Center
  • Xijing Hospital, The Fourth Military Medical University
  • Sichuan Provincial People's Hospital
  • West China Hospital, Sichuan University
  • First Affiliated Hospital of Kunming Medical University
  • The Second Affiliated hospital of Zhejiang University School of Medicine
  • The Second Affiliated Hospital to Nanchang University
  • Nanjing Brain Hospital
  • Tianjin Anding Hospital
  • Tianjin People's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
July 26, 2011
Last Updated
March 7, 2017
Sponsor
Eisai Limited
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1. Study Identification

Unique Protocol Identification Number
NCT01404169
Brief Title
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
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2011 (Actual)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Limited

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Type Dementia
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
260 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
E2020
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to donepezil 5 mg or 10 mg tablets taken orally once daily for 24 weeks.
Primary Outcome Measure Information:
Title
The change in the total Severe Impairment Battery (SIB) score at Week 24
Description
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.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Clinician Interview-Based Impression of Severity (CIBIC)+ overall score at Week 24
Description
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.
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Naoki Kubota
Organizational Affiliation
Neuroscience Clinical Development Section, Japan/Asia Clinical Research Product Creation Unit, Eisai Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
Beijing Anding Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Beijing Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Beijing Huilongguan Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Xuanwu Hospital Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The First Affiliated Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
The Second Affiliated Hospital of Chongqing Medical University
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Guangzhou Brain Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Guangzhou First People's Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
The People's Hospital of Guangxi Zhuang Autonomous Region
City
Nanning
State/Province
Guangxi
Country
China
Facility Name
Tongji Hospital, Tongji Medical College of HUST
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
Union Hospital, Tongji Medical college Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
The Third Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Name
The First People's Hospital of YueYang
City
Yueyang
State/Province
Hunan
Country
China
Facility Name
Qilu Hospital of Shandong University
City
Jinan
State/Province
Shandong
Country
China
Facility Name
The Second Hospital of Shandong University
City
Jinan
State/Province
Shandong
Country
China
Facility Name
The Affiliated Hospital of Medical College Qingdao University
City
Qingdao
State/Province
Shandong
Country
China
Facility Name
Hushan Hospital affliated to Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Renji Hospital, Shanghai Jiaotong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Shanghai Ruijin Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Tangdu Hospital, The Fourth Military Medical University
City
Xi'An
State/Province
Shanxi
Country
China
Facility Name
Xi'An Mental Health Center
City
Xi'An
State/Province
Shanxi
Country
China
Facility Name
Xijing Hospital, The Fourth Military Medical University
City
Xi'An
State/Province
Shanxi
Country
China
Facility Name
Sichuan Provincial People's Hospital
City
Chengdu
State/Province
Sichuan
Country
China
Facility Name
West China Hospital, Sichuan University
City
Chengdu
State/Province
Sichuan
Country
China
Facility Name
First Affiliated Hospital of Kunming Medical University
City
Kunming
State/Province
Yunnan
Country
China
Facility Name
The Second Affiliated hospital of Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
Country
China
Facility Name
The Second Affiliated Hospital to Nanchang University
City
Nanchang
Country
China
Facility Name
Nanjing Brain Hospital
City
Nanjing Jiangsu
Country
China
Facility Name
Tianjin Anding Hospital
City
Tianjin
Country
China
Facility Name
Tianjin People's Hospital
City
Tianjin
Country
China

12. IPD Sharing Statement

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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

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