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The Effectiveness And Safety Of Donepezil Hydrochloride (E2020) In Subjects With Mild To Severe Alzheimer's Disease Residing In An Assisted Living Facility

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ClinicalTrials.gov Identifier: NCT00571064
Recruitment Status : Completed
First Posted : December 11, 2007
Results First Posted : March 12, 2018
Last Update Posted : September 27, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Eisai Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Mild to Severe Alzheimer's Disease
Intervention Drug: Donepezil HCl
Enrollment 97
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description Donepezil HCl 5 milligrams (mg) per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Period Title: Overall Study
Started 97
Completed 76
Not Completed 21
Reason Not Completed
Adverse Event             13
Protocol Violation             4
Withdrawal by Subject             2
Not specified             2
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description Donepezil HCl 5 milligram (mg) per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Baseline Participants 97
Hide Baseline Analysis Population Description
Safety population included all enrolled participants who took at least one dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 97 participants
81.0  (10.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 97 participants
Female
65
  67.0%
Male
32
  33.0%
1.Primary Outcome
Title Mini Mental State Examination (MMSE) Total Scores by Visit
Hide Description The MMSE was a brief test that assessed the cognitive status of the participant. The 30-point test included items that evaluate orientation to time and place, immediate and delayed recall, attention, language, and construction. The total number of correct responses was obtained. The scores ranged from 0 to 30, with higher scores representing better performance. Summaries and analyses in the Intent-to-Treat (ITT) population were carried out using observed cases at each visit. A Study Endpoint evaluation was performed using the last observation carried forward (LOCF) from the open label treatment phase for each participant. The outcome of the study was based on analyses of the primary efficacy variable at Study Endpoint, which was defined as end of study assessment, using the ITT population with LOCF.
Time Frame Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or Early Termination (ET) Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population with LOCF included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 milligram (mg) per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline (Visit 2) 18.7  (5.29)
Week 6 (Visit 3) 20.8  (5.16)
Week 12/ET (Visit 4) 20.5  (5.92)
Week 12 LOCF (Study Endpoint) 20.5  (5.88)
2.Primary Outcome
Title Change From Baseline in MMSE Total Score by Visit
Hide Description The MMSE was a brief test that assessed the cognitive status of the participant. The 30-point test included items that evaluated orientation to time and place, immediate and delayed recall, attention, language, and construction. The total number of correct responses was obtained. The scores ranged from 0 to 30, with higher scores representing better performance. Summaries and analyses in the ITT population were carried out using observed cases at each visit. A Study Endpoint evaluation was performed using the LOCF from the open label treatment phase for each participant. The outcome of the study was based on analyses of the primary efficacy variable at Study Endpoint, which was defined as end of study assessment, using the ITT population with LOCF. Change from Baseline in MMSE Total Score at Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint) has been reported.
Time Frame Baseline, Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 18.7  (5.29)
Change from Baseline at Week 6 (Visit 3) 1.8  (2.81)
Change from Baseline at Week 12/ET (Visit 4) 1.9  (2.79)
Change from Baseline at Week 12 LOCF 1.8  (2.81)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 6 (Visit 3)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12/ET (Visit 4)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12 LOCF (Study Endpoint)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Caregiver Activity Survey (CAS) Total Time by Visit
Hide Description The CAS was a validated tool that measured the time caregivers spent aiding Alzheimer’s participants with their day-to-day activities. The CAS recorded time spent on six activities of daily living, communicating with the person, using transportation, dressing, eating, looking after one’s appearance, and supervising the person. Caregivers were asked to report the amount of time spent on each activity during a 'typical' caregiving day. Total time for the CAS was calculated as the sum of the sub-item times.
Time Frame Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Hours/day
Baseline (Visit 2) 8.9  (8.80)
Week 6 (Visit 3) 9.0  (9.99)
Week 12/ET (Visit 4) 9.0  (9.81)
Week 12 LOCF (Study Endpoint) 9.3  (10.07)
4.Secondary Outcome
Title Change From Baseline in CAS Total Time by Visit
Hide Description The CAS was a validated tool that measured the time caregivers spent aiding Alzheimer’s participants with their day-to-day activities. The CAS recorded time spent on six activities of daily living, communicating with the person, using transportation, dressing, eating, looking after one’s appearance, and supervising the person. Caregivers were asked to report the amount of time spent on each activity during a 'typical' caregiving day. Total time for the CAS was calculated as the sum of the sub-item times. Change from Baseline in CAS Total Time at Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint) has been reported.
Time Frame Baseline, Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at Week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Hours/day
Baseline 8.9  (8.80)
Change from Baseline at Week 6 (Visit 3) 0.3  (6.83)
Change from Baseline at Week 12/ET (Visit 4) 0.3  (5.82)
Change from Baseline at Week 12 LOCF 0.3  (5.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 6 (Visit 3)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6593
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12/ET (Visit 4)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6048
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12 LOCF (Study Endpoint)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5924
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
5.Secondary Outcome
Title Neuropsychiatric Inventory (NPI-8) Total Score by Visit
Hide Description The NPI-8 was an 8-item scale that assessed eight behavioral domains: delusions, hallucinations, agitation, depression, anxiety, apathy, irritability, and aberrant motor behavior. The frequency (0 to 4) and severity (0 to 3) of each domain were assessed; the sub-score for each domain was calculated as the product of the frequency and severity rating. The total score for the NPI was calculated as the sum of the domain sub-score, range from 0 to 96, with higher scores indicating greater behavior disturbances.
Time Frame Baseline (Visit 2), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Visit 2 (Baseline) 5.7  (9.70)
Week 12/ET (Visit 4) 3.9  (5.73)
Week 12 LOCF (Study Endpoint) 3.9  (5.73)
6.Secondary Outcome
Title Change From Baseline in NPI-8 Total Score by Visit
Hide Description The NPI-8 was an 8-item scale that assessed eight behavioral domains: delusions, hallucinations, agitation, depression, anxiety, apathy, irritability, and aberrant motor behavior. The frequency (0 to 4) and severity (0 to 3) of each domain were assessed; the sub-score for each domain was calculated as the product of the frequency and severity rating. The total score for the NPI was calculated as the sum of the domain sub-score, range from 0 to 96, with higher scores indicating greater behavior disturbances. Change from Baseline in NPI-8 Total Score at Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint) has been reported.
Time Frame Baseline, Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 5.7  (9.7)
Change from Baseline at Week 12/ET (Visit 4) -1.8  (8.39)
Change from Baseline at Week 12 LOCF -1.8  (8.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12/ET (Visit 4)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0431
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12 LOCF (Study Endpoint)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0431
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
7.Secondary Outcome
Title Alzheimer Disease-related Quality of Life (ADRQL) Total Score by Visit
Hide Description The ADRQL was an observer-rated quality of life instrument that measured the following domains: social interaction, awareness of self, feelings and mood, enjoyment of activities, and response to surroundings. The ADRQL was a 47-item questionnaire with five domains: relating to and being around other people (ADRQL-A; 12 items), a person’s special identity and important relationships (ADRQL-B; 8 items), different types of behavior (ADRQL-C; 15 items), usual activities (ADRQL-D; 5 items), and behavior in a person’s living environment (ADRQL-E; 7 items). Domain sub-scores were summed to yield a total raw score, which was divided by the total possible score and multiplied by 100 to produce the final score. Each subscale score could be calculated in the similar approach. Total score ranges from 0-100 where higher scores reflected a better quality of life.
Time Frame Baseline (Visit 2), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline (Visit 2) 48.7  (8.71)
Week 12/ET (Visit 4) 47.6  (7.90)
Week 12 LOCF (Study Endpoint) 47.6  (7.90)
8.Secondary Outcome
Title Change From Baseline in ADRQL Total Score by Visit
Hide Description The ADRQL was an observer-rated quality of life instrument that measured the following domains: social interaction, awareness of self, feelings and mood, enjoyment of activities, and response to surroundings. The ADRQL was a 47-item questionnaire with five domains: relating to and being around other people (ADRQL-A; 12 items), a person’s special identity and important relationships (ADRQL-B; 8 items), different types of behavior (ADRQL-C; 15 items), usual activities (ADRQL-D; 5 items), and behavior in a person’s living environment (ADRQL-E; 7 items). Domain sub-scores were summed to yield a total raw score, which was divided by the total possible score and multiplied by 100 to produce the final score. Each subscale score could be calculated in the similar approach. Higher scores reflected a better quality of life. Change from Baseline in ADRQL Total Score at Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint) has been reported.
Time Frame Baseline, Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 48.7  (8.71)
Change from Baseline at Week 12/ET (Visit 4) -1.1  (6.93)
Change from Baseline at Week 12 LOCF -1.1  (6.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12/ET (Visit 4)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1285
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12 LOCF (Study Endpoint)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1285
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Disability Assessment in Dementia (DAD) Total Score by Visit
Hide Description The DAD was a 10 domain 40-item scale that measured a participant’s ability to initiate, plan, organize, and perform both basic and instrumental activities of daily living. These domains were: hygiene (7 items), dressing (5 items), continence (2 items), eating (3 items), meal preparation (3 items), telephoning (4 items), going on an outing (5 items), finance (4 items), medication (2 items), and leisure (5 items). The three responses to the DAD items were “No, Yes, and N/A”. A “No” answer scored 0 and a “Yes” answer scored 1. The scoring range was 0-40, with a higher score indicating less disability (better quality of life). If N/A was selected then it was treated as missing. When there were items with missing values, the domain sub-scores and the total score were imputed. Domain sub-scores were summed to yield a total raw score. This was divided by the total possible score and multiplied by 100 to produce the final score. Each subscale score can be calculated in the similar approach.
Time Frame Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline (Visit 2) 58.3  (26.48)
Week 6 (Visit 3) 58.4  (24.93)
Week 12/ET (Visit 4) 57.2  (25.53)
Week 12 LOCF (Study Endpoint) 57.2  (25.39)
10.Secondary Outcome
Title Change From Baseline in DAD Total Score by Visit
Hide Description The DAD was a 10 domain 40-item scale that measured a participant’s ability to initiate, plan, organize, and perform both basic and instrumental activities of daily living. These domains were: hygiene (7 items), dressing (5 items), continence (2 items), eating (3 items), meal preparation (3 items), telephoning (4 items), going on an outing (5 items), finance (4 items), medication (2 items), and leisure (5 items). The three responses to the DAD items were “No, Yes, and N/A”. A “No” answer scored 0 and a “Yes” answer scored 1. The scoring range was 0-40, with a higher score indicating less disability (better quality of life). If N/A was selected then it was treated as missing. When there were items with missing values, the domain sub-scores and the total score were imputed. Domain sub-scores were summed to yield a total raw score. This was divided by the total possible score and multiplied by 100 to produce the final score. Each subscale score can be calculated in the similar approach.
Time Frame Baselinw, Week 6 (Visit 3) and Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population included all enrolled participants who took at least one dose of study medication, and had baseline and at least one post-baseline assessment of at least one efficacy variable. Study endpoint evaluation at week 12 included ITT population with LOCF.
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description:
Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
Overall Number of Participants Analyzed 93
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 58.3  (26.48)
Change from Baseline at Week 6 (Visit 2) -1.1  (8.52)
Change from Baseline at Week 12/ET (Visit 4) -1.1  (14.38)
Change from Baseline at Week 12 LOCF -1.1  (14.30)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 6 (Visit 3)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2327
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12/ET (Visit 4)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4724
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Donepezil Hydrochloride (HCl)
Comments Week 12 LOCF - Study Endpoint
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4724
Comments Significance level of 0.05
Method t-test, 2 sided
Comments [Not Specified]
Time Frame All adverse events (AEs) and serious adverse events (SAEs) were collected from Screening Visit 1 (-21 to -14 days) until Week 12 Visit 4 (Day 84) or early termination. AEs/SAEs were collected for approximately 4 months.
Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events were reported. TEAEs were defined as events that occurred after the first dose of study drug or a pre-existing condition that worsened after starting study drug. The safety population was analyzed and included enrolled participants who received at least one dose of study drug.
 
Arm/Group Title Donepezil Hydrochloride (HCl)
Hide Arm/Group Description Donepezil HCl 5 mg per day (one 5 mg tablet) was administered for the first 6 weeks (42 days), and then the dose was increased to 10 mg/day (two 5 mg tablets). If 10 mg of donepezil was not tolerated, the dosage was reduced temporarily to 5 mg. The participant was re-challenged with 10 mg of study drug within 5 to 7 days. If the participant still could not tolerate the higher dose after re-challenge, they continued in the study on 5 mg per day of study drug.
All-Cause Mortality
Donepezil Hydrochloride (HCl)
Affected / at Risk (%)
Total   2/97 (2.06%) 
Show Serious Adverse Events Hide Serious Adverse Events
Donepezil Hydrochloride (HCl)
Affected / at Risk (%)
Total   12/97 (12.37%) 
Cardiac disorders   
Atrioventricular block complete † 1  1/97 (1.03%) 
Cardiac arrest † 1  1/97 (1.03%) 
Gastrointestinal disorders   
Abdominal pain † 1  1/97 (1.03%) 
Gastric volvulus † 1  1/97 (1.03%) 
Intestinal obstruction † 1  1/97 (1.03%) 
Infections and infestations   
Cellulitis † 1  1/97 (1.03%) 
Septic shock † 1  1/97 (1.03%) 
Urinary tract infection † 1  1/97 (1.03%) 
Injury, poisoning and procedural complications   
Hip fracture † 1  1/97 (1.03%) 
Spinal compression fracture † 1  1/97 (1.03%) 
Metabolism and nutrition disorders   
Dehydration † 1  1/97 (1.03%) 
Diabetes mellitus † 1  1/97 (1.03%) 
Musculoskeletal and connective tissue disorders   
Muscle mass † 1  1/97 (1.03%) 
Nervous system disorders   
Metabolic encephalopathy † 1  1/97 (1.03%) 
Psychiatric disorders   
Alcohol abuse † 1  1/97 (1.03%) 
Renal and urinary disorders   
Renal failure acute † 1  1/97 (1.03%) 
Reproductive system and breast disorders   
Benign prostatic hyperplasia † 1  1/97 (1.03%) 
Respiratory, thoracic and mediastinal disorders   
Asthma † 1  1/97 (1.03%) 
Epistaxis † 1  1/97 (1.03%) 
Vascular disorders   
Deep vein thrombosis † 1  1/97 (1.03%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Donepezil Hydrochloride (HCl)
Affected / at Risk (%)
Total   56/97 (57.73%) 
Gastrointestinal disorders   
Nausea † 1  9/97 (9.28%) 
Diarrhoea † 1  8/97 (8.25%) 
Vomiting † 1  4/97 (4.12%) 
Abdominal pain † 1  2/97 (2.06%) 
General disorders   
Irritability † 1  2/97 (2.06%) 
Oedema peripheral † 1  2/97 (2.06%) 
Infections and infestations   
Urinary tract infection † 1  4/97 (4.12%) 
Nasopharyngitis † 1  2/97 (2.06%) 
Injury, poisoning and procedural complications   
Fall † 1  2/97 (2.06%) 
Investigations   
Weight decreased † 1  2/97 (2.06%) 
Metabolism and nutrition disorders   
Decreased appetite † 1  2/97 (2.06%) 
Musculoskeletal and connective tissue disorders   
Back pain † 1  2/97 (2.06%) 
Nervous system disorders   
Dizziness † 1  3/97 (3.09%) 
Headache † 1  3/97 (3.09%) 
Psychiatric disorders   
Depression † 1  2/97 (2.06%) 
Renal and urinary disorders   
Urinary incontinence † 1  2/97 (2.06%) 
Respiratory, thoracic and mediastinal disorders   
Cough † 1  4/97 (4.12%) 
Skin and subcutaneous tissue disorders   
Rash † 1  3/97 (3.09%) 
1
Term from vocabulary, MedDRA
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Eisai Medical Services
Organization: Eisai Inc.
Phone: 1-888-422-4743
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Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT00571064     History of Changes
Other Study ID Numbers: E2020-A001-415
First Submitted: December 6, 2007
First Posted: December 11, 2007
Results First Submitted: February 7, 2018
Results First Posted: March 12, 2018
Last Update Posted: September 27, 2018