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

Alzheimer's Type Dementia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01404169
• Other study ID #: E2020-C086-339
• Status: Completed
• Phase: Phase 3
• First received: July 26, 2011
• Last updated: March 7, 2017
• Start date: September 2011
• Est. completion date: September 2014

Study information

• Verified date: March 2017
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: September 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Type Dementia
• Dementia

Intervention

Drug:
• E2020
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.
• Placebo
Placebo matched to donepezil 5 mg or 10 mg tablets taken orally once daily for 24 weeks.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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