Alzheimer's Disease, Vascular Dementia
Conditions
Keywords
Aricept® Evess, non-interventional study, Alzheimer's Disease, Vascular Dementia, efficacy, tolerability, safety.
Brief summary
The Aricept® Evess study is a prospective, non-comparative, non-interventional study on use of Aricept® Evess in the treatment of out-patients with AD and Vascular Dementia. The 24 week length of the study aims to collect data from a large number of patients (n= 400) on the safety and efficacy at the usual dosage of the product providing an overview of Aricept® Evess profile.
Interventions
DRUGAricept® Evess
5 mg film-coated orodispersible tablets, 10 mg film-coated orodispersible tablets. Treatment may be started with 5 mg donepezil/ day (once-a-day dosing) and after four weeks can be titrated to 10 mg/day (once-a-day dosing).
Sponsors
Pfizer
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Outpatients (male / female), older than 50 years. * Patients with clinical symptoms of mild and moderate AD and Vascular Dementia. * MMSE score between 12 - 24.
Exclusion criteria
* Patients with a known hypersensitivity to donepezil clorhydrat, piperidine derivatives or any of the excipients of Aricept® Evess. * Patients with severe impaired hepatic function. * Patients with pre-existing gastrointestinal ulcer disease. * Patients with the history of bronchial asthma or chronic obstructive lung disease. * Patients with the history of serious atrioventricular conduction disturbances.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mini Mental State Examination (MMSE) Total at Week 24 Last Observation Carried Forward (LOCF) | Baseline and Week 24 | MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, higher score indicated better cognitive state. Change: mean score at Week 24 LOCF minus mean score at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in MMSE Total | Baseline, Week 8, 16, and 24 | MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, higher score indicated better cognitive state. Change: least squares (LS) mean score at observation minus LS mean score at baseline. Changes from baseline at each week were controlled for baseline MMSE. |
| Change From Baseline in Functional Activity Questionnaire (FAQ) | Baseline and Week 24 | Participants completed the FAQ for physical function. Overall scores could have ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function. Change from baseline was to be calculated as baseline scores minus week 24 scores. |
| Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Week 8 | CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Week 16 | CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Week 24 | CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
| Number of Participants in Each Patient Domain of Benefit | Week 24 | Participants asked to indicate if the cognition, functionality, and/or behavior domain were most benefited/improved after treatment (dichotomous yes/no endpoints where checking the CRF box next to each domain indicated 'yes' and leaving a box blank indicated 'no'). |
| Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Week 24 | CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Tolerability | Week 24 | Overall Evaluation of Tolerability at Week 24; 1=Very good, 2=Good, 3=Moderate, 4=Poor |
| Number of Participants Receiving Other Medications | Baseline and Week 24 | Information collected and recorded by investigator in accordance with existing medical records. World Health Organization- Drug (WHO-Drug) coding dictionary applied. |
Countries
Romania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donepezil 5 milligrams per day (mg/day), once-a-day dosing and after 4 weeks titrated to 10 mg/day, once-a-day dosing | 370 |
| Total | 370 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Death | 3 |
| Overall Study | Lost to Follow-up | 19 |
| Overall Study | No longer willing to participant in stud | 4 |
| Overall Study | Other | 4 |
Baseline characteristics
| Characteristic | Donepezil |
|---|---|
| Age, Customized 65 to 74 years | 130 Participants |
| Age, Customized 75 to 84 years | 142 Participants |
| Age, Customized Greater than or equal to 85 years | 27 Participants |
| Age, Customized Less than 65 years | 71 Participants |
| Sex: Female, Male Female | 200 Participants |
| Sex: Female, Male Male | 170 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 370 |
| serious Total, serious adverse events | 12 / 370 |
Outcome results
Primary
Change From Baseline in Mini Mental State Examination (MMSE) Total at Week 24 Last Observation Carried Forward (LOCF)
MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, higher score indicated better cognitive state. Change: mean score at Week 24 LOCF minus mean score at baseline.
Time frame: Baseline and Week 24
Population: Full Analysis Set (FAS): all participants who received at least 1 dose of Donepezil and had at least 1 postbaseline efficacy evaluation. LOCF was used. N=number of participants with evaluable data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Donepezil | Change From Baseline in Mini Mental State Examination (MMSE) Total at Week 24 Last Observation Carried Forward (LOCF) | 1.92 Scores on a scale | Standard Error 0.14 |
95% CI: [1.65, 2.2]
Secondary
Change From Baseline in Functional Activity Questionnaire (FAQ)
Participants completed the FAQ for physical function. Overall scores could have ranged from 0 (independent) to 30 (dependent) where lower scores represented an improvement in physical function. Change from baseline was to be calculated as baseline scores minus week 24 scores.
Time frame: Baseline and Week 24
Population: FAS. Data not analyzed
Secondary
Change From Baseline in MMSE Total
MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, higher score indicated better cognitive state. Change: least squares (LS) mean score at observation minus LS mean score at baseline. Changes from baseline at each week were controlled for baseline MMSE.
Time frame: Baseline, Week 8, 16, and 24
Population: FAS. N=number of participants with evaluable data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change From Baseline in MMSE Total | Week 8 (N=348) | 0.92 Scores on a scale | Standard Error 0.09 |
| Donepezil | Change From Baseline in MMSE Total | Week 16 (N=340) | 1.56 Scores on a scale | Standard Error 0.12 |
| Donepezil | Change From Baseline in MMSE Total | Week 24 (N=327) | 1.97 Scores on a scale | Standard Error 0.14 |
95% CI: [0.75, 1.08]
95% CI: [1.32, 1.8]
95% CI: [1.69, 2.25]
Secondary
Number of Participants in Each Patient Domain of Benefit
Participants asked to indicate if the cognition, functionality, and/or behavior domain were most benefited/improved after treatment (dichotomous yes/no endpoints where checking the CRF box next to each domain indicated 'yes' and leaving a box blank indicated 'no').
Time frame: Week 24
Population: Safety population: all participants who received at least 1 dose of study drug. N=number of participants with evaluable data. Week 24 LOCF not reported as data only collected at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants in Each Patient Domain of Benefit | Cognition | 202 Participants |
| Donepezil | Number of Participants in Each Patient Domain of Benefit | Functionality | 215 Participants |
| Donepezil | Number of Participants in Each Patient Domain of Benefit | Behavior | 193 Participants |
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16
CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Week 16
Population: FAS. N=number of participants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Very much improved | 21 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Much improved | 119 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Minimally improved | 116 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | No change | 66 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Minimally worse | 17 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 16 | Much worse | 2 Participants |
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24
CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Week 24
Population: FAS. N=number of participants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Very much improved | 33 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Much improved | 129 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Minimally improved | 87 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | No change | 62 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Minimally worse | 16 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Much worse | 2 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 | Very much worse | 1 Participants |
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF
CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Week 24
Population: FAS; LOCF. N=number of participants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Very much improved | 34 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Much improved | 133 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Minimally improved | 95 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | No change | 70 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Minimally worse | 17 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Much worse | 2 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 24 LOCF | Very much worse | 1 Participants |
Secondary
Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8
CGI-I: 7-point Investigator-rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement was defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected.
Time frame: Week 8
Population: FAS. N=number of participants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Very much improved | 5 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Much improved | 68 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Minimally improved | 194 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | No change | 74 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Minimally worse | 8 Participants |
| Donepezil | Number of Participants With Categorical Scores on Clinical Global Impression - Improvement (CGI-I) at Week 8 | Much worse | 2 Participants |
Other Pre-specified
Number of Participants Receiving Other Medications
Information collected and recorded by investigator in accordance with existing medical records. World Health Organization- Drug (WHO-Drug) coding dictionary applied.
Time frame: Baseline and Week 24
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants Receiving Other Medications | Baseline | 205 Participants |
| Donepezil | Number of Participants Receiving Other Medications | Week 24 | 270 Participants |
Other Pre-specified
Number of Participants With Treatment Tolerability
Overall Evaluation of Tolerability at Week 24; 1=Very good, 2=Good, 3=Moderate, 4=Poor
Time frame: Week 24
Population: Safety population; N=number of particpants with evaluable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Number of Participants With Treatment Tolerability | Very Good | 186 Participants |
| Donepezil | Number of Participants With Treatment Tolerability | Good | 130 Participants |
| Donepezil | Number of Participants With Treatment Tolerability | Moderate | 14 Participants |
| Donepezil | Number of Participants With Treatment Tolerability | Poor | 1 Participants |