Trial Outcomes & Findings for The Effectiveness And Safety Of Donepezil Hydrochloride (E2020) In Subjects With Mild To Severe Alzheimer's Disease Residing In An Assisted Living Facility (NCT NCT00571064)
NCT ID: NCT00571064
Last Updated: 2018-09-27
Results Overview
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.
COMPLETED
PHASE4
97 participants
Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or Early Termination (ET) Visit, Week 12 LOCF (Study Endpoint)
2018-09-27
Participant Flow
Participant milestones
| Measure |
Donepezil Hydrochloride (HCl)
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.
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|---|---|
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Overall Study
STARTED
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97
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Overall Study
COMPLETED
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76
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Overall Study
NOT COMPLETED
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21
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Reasons for withdrawal
| Measure |
Donepezil Hydrochloride (HCl)
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.
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|---|---|
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Overall Study
Adverse Event
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13
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Overall Study
Protocol Violation
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4
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Overall Study
Withdrawal by Subject
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2
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Overall Study
Other
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2
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Baseline Characteristics
The Effectiveness And Safety Of Donepezil Hydrochloride (E2020) In Subjects With Mild To Severe Alzheimer's Disease Residing In An Assisted Living Facility
Baseline characteristics by cohort
| Measure |
Donepezil Hydrochloride (HCl)
n=97 Participants
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.
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|---|---|
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Age, Continuous
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81.0 Years
STANDARD_DEVIATION 10.30 • n=5 Participants
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Sex: Female, Male
Female
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65 Participants
n=5 Participants
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Sex: Female, Male
Male
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32 Participants
n=5 Participants
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PRIMARY outcome
Timeframe: Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or Early Termination (ET) Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Mini Mental State Examination (MMSE) Total Scores by Visit
Baseline (Visit 2)
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18.7 Scores on a scale
Standard Deviation 5.29
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Mini Mental State Examination (MMSE) Total Scores by Visit
Week 6 (Visit 3)
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20.8 Scores on a scale
Standard Deviation 5.16
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Mini Mental State Examination (MMSE) Total Scores by Visit
Week 12/ET (Visit 4)
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20.5 Scores on a scale
Standard Deviation 5.92
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Mini Mental State Examination (MMSE) Total Scores by Visit
Week 12 LOCF (Study Endpoint)
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20.5 Scores on a scale
Standard Deviation 5.88
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PRIMARY outcome
Timeframe: Baseline, Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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|---|---|
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Change From Baseline in MMSE Total Score by Visit
Baseline
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18.7 Scores on a scale
Standard Deviation 5.29
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Change From Baseline in MMSE Total Score by Visit
Change from Baseline at Week 6 (Visit 3)
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1.8 Scores on a scale
Standard Deviation 2.81
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Change From Baseline in MMSE Total Score by Visit
Change from Baseline at Week 12/ET (Visit 4)
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1.9 Scores on a scale
Standard Deviation 2.79
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Change From Baseline in MMSE Total Score by Visit
Change from Baseline at Week 12 LOCF
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1.8 Scores on a scale
Standard Deviation 2.81
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SECONDARY outcome
Timeframe: Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Caregiver Activity Survey (CAS) Total Time by Visit
Baseline (Visit 2)
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8.9 Hours/day
Standard Deviation 8.80
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Caregiver Activity Survey (CAS) Total Time by Visit
Week 6 (Visit 3)
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9.0 Hours/day
Standard Deviation 9.99
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Caregiver Activity Survey (CAS) Total Time by Visit
Week 12/ET (Visit 4)
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9.0 Hours/day
Standard Deviation 9.81
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Caregiver Activity Survey (CAS) Total Time by Visit
Week 12 LOCF (Study Endpoint)
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9.3 Hours/day
Standard Deviation 10.07
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SECONDARY outcome
Timeframe: Baseline, Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Change From Baseline in CAS Total Time by Visit
Baseline
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8.9 Hours/day
Standard Deviation 8.80
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Change From Baseline in CAS Total Time by Visit
Change from Baseline at Week 6 (Visit 3)
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0.3 Hours/day
Standard Deviation 6.83
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Change From Baseline in CAS Total Time by Visit
Change from Baseline at Week 12/ET (Visit 4)
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0.3 Hours/day
Standard Deviation 5.82
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Change From Baseline in CAS Total Time by Visit
Change from Baseline at Week 12 LOCF
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0.3 Hours/day
Standard Deviation 5.78
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SECONDARY outcome
Timeframe: Baseline (Visit 2), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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|---|---|
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Neuropsychiatric Inventory (NPI-8) Total Score by Visit
Visit 2 (Baseline)
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5.7 Scores on a scale
Standard Deviation 9.70
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Neuropsychiatric Inventory (NPI-8) Total Score by Visit
Week 12/ET (Visit 4)
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3.9 Scores on a scale
Standard Deviation 5.73
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Neuropsychiatric Inventory (NPI-8) Total Score by Visit
Week 12 LOCF (Study Endpoint)
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3.9 Scores on a scale
Standard Deviation 5.73
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SECONDARY outcome
Timeframe: Baseline, Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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|---|---|
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Change From Baseline in NPI-8 Total Score by Visit
Baseline
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5.7 Scores on a scale
Standard Deviation 9.7
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Change From Baseline in NPI-8 Total Score by Visit
Change from Baseline at Week 12/ET (Visit 4)
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-1.8 Scores on a scale
Standard Deviation 8.39
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Change From Baseline in NPI-8 Total Score by Visit
Change from Baseline at Week 12 LOCF
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-1.8 Scores on a scale
Standard Deviation 8.39
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SECONDARY outcome
Timeframe: Baseline (Visit 2), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Alzheimer Disease-related Quality of Life (ADRQL) Total Score by Visit
Baseline (Visit 2)
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48.7 Scores on a scale
Standard Deviation 8.71
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Alzheimer Disease-related Quality of Life (ADRQL) Total Score by Visit
Week 12/ET (Visit 4)
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47.6 Scores on a scale
Standard Deviation 7.90
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Alzheimer Disease-related Quality of Life (ADRQL) Total Score by Visit
Week 12 LOCF (Study Endpoint)
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47.6 Scores on a scale
Standard Deviation 7.90
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SECONDARY outcome
Timeframe: Baseline, Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Change From Baseline in ADRQL Total Score by Visit
Baseline
|
48.7 Scores on a scale
Standard Deviation 8.71
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Change From Baseline in ADRQL Total Score by Visit
Change from Baseline at Week 12/ET (Visit 4)
|
-1.1 Scores on a scale
Standard Deviation 6.93
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Change From Baseline in ADRQL Total Score by Visit
Change from Baseline at Week 12 LOCF
|
-1.1 Scores on a scale
Standard Deviation 6.93
|
SECONDARY outcome
Timeframe: Baseline (Visit 2), Week 6 (Visit 3), Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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Disability Assessment in Dementia (DAD) Total Score by Visit
Baseline (Visit 2)
|
58.3 Scores on a scale
Standard Deviation 26.48
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Disability Assessment in Dementia (DAD) Total Score by Visit
Week 6 (Visit 3)
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58.4 Scores on a scale
Standard Deviation 24.93
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Disability Assessment in Dementia (DAD) Total Score by Visit
Week 12/ET (Visit 4)
|
57.2 Scores on a scale
Standard Deviation 25.53
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Disability Assessment in Dementia (DAD) Total Score by Visit
Week 12 LOCF (Study Endpoint)
|
57.2 Scores on a scale
Standard Deviation 25.39
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SECONDARY outcome
Timeframe: Baselinw, Week 6 (Visit 3) and Week 12 (Visit 4) or ET Visit, Week 12 LOCF (Study Endpoint)Population: 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.
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.
Outcome measures
| Measure |
Donepezil Hydrochloride (HCl)
n=93 Participants
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.
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|---|---|
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Change From Baseline in DAD Total Score by Visit
Baseline
|
58.3 Scores on a scale
Standard Deviation 26.48
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Change From Baseline in DAD Total Score by Visit
Change from Baseline at Week 6 (Visit 2)
|
-1.1 Scores on a scale
Standard Deviation 8.52
|
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Change From Baseline in DAD Total Score by Visit
Change from Baseline at Week 12/ET (Visit 4)
|
-1.1 Scores on a scale
Standard Deviation 14.38
|
|
Change From Baseline in DAD Total Score by Visit
Change from Baseline at Week 12 LOCF
|
-1.1 Scores on a scale
Standard Deviation 14.30
|
Adverse Events
Donepezil Hydrochloride (HCl)
Serious adverse events
| Measure |
Donepezil Hydrochloride (HCl)
n=97 participants at risk
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.
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|---|---|
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Cardiac disorders
Atrioventricular block complete
|
1.0%
1/97 • 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.
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.
|
|
Cardiac disorders
Cardiac arrest
|
1.0%
1/97 • 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.
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.
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
1/97 • 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.
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.
|
|
Gastrointestinal disorders
Gastric volvulus
|
1.0%
1/97 • 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.
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.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.0%
1/97 • 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.
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.
|
|
Infections and infestations
Cellulitis
|
1.0%
1/97 • 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.
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.
|
|
Infections and infestations
Septic shock
|
1.0%
1/97 • 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.
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.
|
|
Infections and infestations
Urinary tract infection
|
1.0%
1/97 • 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.
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.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
1.0%
1/97 • 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.
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.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
1.0%
1/97 • 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.
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.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.0%
1/97 • 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.
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.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
1.0%
1/97 • 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.
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.
|
|
Musculoskeletal and connective tissue disorders
Muscle mass
|
1.0%
1/97 • 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.
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.
|
|
Nervous system disorders
Metabolic encephalopathy
|
1.0%
1/97 • 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.
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.
|
|
Psychiatric disorders
Alcohol abuse
|
1.0%
1/97 • 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.
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.
|
|
Renal and urinary disorders
Renal failure acute
|
1.0%
1/97 • 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.
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.
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
1.0%
1/97 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
1.0%
1/97 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.0%
1/97 • 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.
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.
|
|
Vascular disorders
Deep vein thrombosis
|
1.0%
1/97 • 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.
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.
|
Other adverse events
| Measure |
Donepezil Hydrochloride (HCl)
n=97 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Nausea
|
9.3%
9/97 • 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.
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
8.2%
8/97 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.1%
4/97 • 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.
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.
|
|
Infections and infestations
Urinary tract infection
|
4.1%
4/97 • 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.
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.
|
|
Gastrointestinal disorders
Vomiting
|
4.1%
4/97 • 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.
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.
|
|
Nervous system disorders
Dizziness
|
3.1%
3/97 • 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.
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.
|
|
Nervous system disorders
Headache
|
3.1%
3/97 • 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.
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.1%
2/97 • 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.
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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.1%
2/97 • 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.
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.
|
|
Psychiatric disorders
Depression
|
2.1%
2/97 • 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.
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.
|
|
Injury, poisoning and procedural complications
Fall
|
2.1%
2/97 • 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.
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.
|
|
General disorders
Irritability
|
2.1%
2/97 • 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.
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.
|
|
Infections and infestations
Nasopharyngitis
|
2.1%
2/97 • 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.
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.
|
|
General disorders
Oedema peripheral
|
2.1%
2/97 • 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.
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.
|
|
Renal and urinary disorders
Urinary incontinence
|
2.1%
2/97 • 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.
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.
|
|
Investigations
Weight decreased
|
2.1%
2/97 • 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.
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.1%
3/97 • 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.
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.
|
|
Gastrointestinal disorders
Abdominal pain
|
2.1%
2/97 • 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.
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.
|
Additional Information
Eisai Medical Services
Eisai Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER