Dementia, Mixed, Dementia, Vascular
Conditions
Brief summary
To document effectiveness, safety, and tolerability of donepezil in patients with mixed AD/VaD, and to further document the effectiveness, safety, and tolerability of donepezil in patients with VaD. The effects of donepezil on executive functioning, behavior, general cognition, ADLs and global functioning will be assessed.
Detailed description
The trial was terminated on October 15, 2007 due to difficulties in recruiting the subjects. There were no safety or efficacy concerns regarding the study medication in the decision to terminate the trial.
Interventions
DRUGDonepezil
donepezil 5mg/day for 6 weeks and then 5 to 10mg/day for 18 weeks
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet DSM-IV-TR criteria for the clinical diagnosis of Vascular Dementia or the clinical diagnosis of dementia due to multiple etiologies. * Subjects must have a reliable caregiver or family member who agrees to accompany the subject to all scheduled visits, provide information about the subject as required.
Exclusion criteria
* Subjects with any current primary psychiatric diagnosis other than dementia of the Alzheimer's type or Vascular Dementia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set | Baseline, week 12, week 24 | Change from baseline in sMMSE total score. Change: mean total score at observation minus mean total score at baseline. Total score is derived by adding all subscores and ranges from 0 to 30; a higher score indicates a better cognitive state. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CLOX Differential Score Change From Baseline; Full Analysis Set (FAS) | Baseline, 12 weeks, 24 weeks | CLOX differential score equals the difference between the score for CLOX 2 and the score for CLOX 1, values range from 15 to 0, with 0 indicating perfect executive function, and a worsening with the increasing score. |
| Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain. | Baseline, 12 weeks, 24 weeks | IADL domain consists of 23 yes-no questions on 6 items (meal preparation, telephoning, going out, finance & correspondence, medications, leisure & housework. Change: Mean IADL score at observation minus mean IADL score at baseline. Total IADL score = number of questions answered yes multiplied by 100 divided by total number of questions answered |
| Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS) | Baseline, week 12, week 24 | DAD total score equals total number of questions answered yes multiplied by 100 divided by total number of questions answered. |
| Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS) | Baseline, 12 weeks, 24 weeks | The ability to draw a clock free-hand. Scored on a scale from 1 to 15; lower scores indicate higher impairment. Change: Mean CLOX 1 score at observation minus mean CLOX score at baseline. |
| Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS) | Baseline, 12 weeks, 24 weeks | The ability to copy a drawing of a clock. Scored on a scale from 1 to 15; lower scores indicate higher impairment. Change: Mean CLOX 2 score at observation minus mean CLOX 2 score at baseline. |
| Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS) | Baseline, 12 weeks, week 24 | The number of words a particpant can generate in 1 minute. |
| Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain. | Baseline, week 12, week 24 | The ADL domain includes 17 yes/no questions on four items (hygiene, dressing, continence, eating). Score equals number of questions answered yes multiplied by 100 divided by number of questions answered. Change: Mean ADL score at observation minus mean ADL score at baseline. |
| Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS) | Baseline, week 12, week 24 | The total NPI-Q-D score is equal to the sum of all indiviudal symptom distress scale scores with a range of 0 to 60 |
| Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS) | Baseline, week 24 | Scale measures subject's clinical condition at baseline for severity (CGI-S) & for improvement from baseline (CGI-I). At baseline subject rated on numerical scale, 1 (not at all ill) to 7 (most extremely ill). At follow up subject rated on 7 point Likert scale from 1(very much improved) to 7(very much worse) & 4 indicates no change from baseline |
| Clinical Global Impressions Severity (CGI-S) | Baseline | Scale measures subject's clinical condition at baseline for severity (CGI-S) subject rated on numerical scale, 1 (not at all ill) to 7 (most extremely ill). |
| Clinical Global Impressions Improvement (CGI-I) | Week (wk) 24 | Scale measures subject's clinical condition for improvement from baseline (CGI-I)subject rated on 7 point Likert scale from 1(very much improved) to 7(very much worse) & 4 indicates no change from baseline |
| Clinical Global Impressions Improvement (CGI-I) Dichotomized Response | Baseline, week 24 | Scale measures subject's (CGI-I) rated on categorial 7 point Likert scale 1 (very much improved) to 7 (very much worse) with 4 indicating no change from baseline. A dichotomized variable was created: responder = CGI-I score of 4 or less; non-responder = CGI-I score of 5 or more |
| Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS) | Baseline, 12 weeks, 24 weeks | NPI-Q measures severity of behavioural manifestations of dementia & the level of distress each symptom gives the main caregiver, 1 (mild), 3 (severe), 0 if symptom absent, NPI-Q also measures the caregiver distress associated with each symptom,0(no distress)to 5(very severe), total score equals sum of individual item scores & ranges from 0 to 36 |
Countries
Canada
Participant flow
Recruitment details
Study was conducted in Canada in 30 centres.
Participants by arm
| Arm | Count |
|---|---|
| Donepezil Subjects received open-label donepezil treatment with 5 mg administered per os (orally; PO)quaque die (every day; QD) for 6 weeks. Donepezil was increased to 10 mg QD (the maximum dose)at the Week-6 visit for an additional planned 18 weeks. | 149 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Arrived early for last visit in error | 1 |
| Overall Study | Death | 2 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Protocol Violation | 3 |
| Overall Study | Subject felt pill not effective enough | 1 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Donepezil |
|---|---|
| Age, Customized < 45 | 0 Participants |
| Age, Customized 45-64 | 20 Participants |
| Age, Customized >= 65 | 129 Participants |
| Sex: Female, Male Female | 82 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 53 / — |
| serious Total, serious adverse events | 24 / — |
Outcome results
Primary
Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set
Change from baseline in sMMSE total score. Change: mean total score at observation minus mean total score at baseline. Total score is derived by adding all subscores and ranges from 0 to 30; a higher score indicates a better cognitive state.
Time frame: Baseline, week 12, week 24
Population: Full Analysis Set (FAS):all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. N=137; Weeks 12, 24 n=124, 114
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set | Week 12 (n=124) | 0.41 Score on a scale | Standard Deviation 3.1 |
| Donepezil | Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set | Week 24 (n=114) | 0.69 Score on a scale | Standard Deviation 3.2 |
| Donepezil | Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set | Week 24 LOCF (n=137) | 0.48 Score on a scale | Standard Deviation 3.25 |
Comparison: Week 12 Null hypothesis; change from baseline to the final visit = 0. Alternative hypothesis; change from baseline to final visit not = to 0. Sample of 260 participants was required for study to have 85% power to detect change from baseline to final visit of 0.73 in SMMSE total score, with a SD of 3.5. Fewer than 260 patients were enrolled, due to this loss in power the number of analyses specified in the protocol has been reduced and any analyses carried out will be exploratory in nature.p-value: 0.18295% CI: [-0.21, 1.09]Mixed Models Analysis
Comparison: Week 24 Null hypothesis; change from baseline to the final visit = 0. Alternative hypothesis; change from baseline to final visit not = to 0. Sample of 260 participants was required for study to have 85% power to detect change from baseline to final visit of 0.73 in SMMSE total score, with a SD of 3.5. Fewer than 260 patients were enrolled, due to this loss in power the number of analyses specified in the protocol has been reduced and any analyses carried out will be exploratory in nature.p-value: 0.06795% CI: [-0.05, 1.36]Mixed Models Analysis
Comparison: Week 24 LOCF Null hypothesis; change from baseline to the final visit = 0. Alternative hypothesis; change from baseline to final visit not = to 0. Sample of 260 participants was required for study to have 85% power to detect change from baseline to final visit of 0.73 in SMMSE total score, with a SD of 3.5. Fewer than 260 patients were enrolled, due to this loss in power the number of analyses specified in the protocol has been reduced and any analyses carried out will be exploratory in nature.p-value: 0.085Mixed Models Analysis
Secondary
Clinical Global Impressions Improvement (CGI-I)
Scale measures subject's clinical condition for improvement from baseline (CGI-I)subject rated on 7 point Likert scale from 1(very much improved) to 7(very much worse) & 4 indicates no change from baseline
Time frame: Week (wk) 24
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. n=number of subjects with value (Week 24 n=116; Week 24 LOCF n=136)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Very much worse (n=116) | 0 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Very much improved (n=136) | 4 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Much improved (n=136) | 27 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Minimally improved (n=136) | 49 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF No change (n=136) | 30 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Minimally worse (n=136) | 19 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Much worse (n=136) | 7 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 LOCF Very much worse (n=136) | 0 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Very much improved (n=116) | 3 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Much improved (n=116) | 27 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Minimally improved (n=116) | 44 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 No change (n=116) | 21 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Minimally worse (n=116) | 14 Participants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) | Wk 24 Much worse (n=116) | 7 Participants |
Secondary
Clinical Global Impressions Improvement (CGI-I) Dichotomized Response
Scale measures subject's (CGI-I) rated on categorial 7 point Likert scale 1 (very much improved) to 7 (very much worse) with 4 indicating no change from baseline. A dichotomized variable was created: responder = CGI-I score of 4 or less; non-responder = CGI-I score of 5 or more
Time frame: Baseline, week 24
Population: Full Analysis Set (FAS):all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy. LOCF = Last Observation Carried Forward. Week 24 n=116; Week 24 LOCF n=136
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Clinical Global Impressions Improvement (CGI-I) Dichotomized Response | Week 24 Responder (n=116) | 95 Particpants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) Dichotomized Response | Week 24 Non-responder (n=116) | 21 Particpants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) Dichotomized Response | Week 24 LOCF Responder (n=136) | 110 Particpants |
| Donepezil | Clinical Global Impressions Improvement (CGI-I) Dichotomized Response | Week 24 LOCF Non-responder (n=136) | 26 Particpants |
Secondary
Clinical Global Impressions Severity (CGI-S)
Scale measures subject's clinical condition at baseline for severity (CGI-S) subject rated on numerical scale, 1 (not at all ill) to 7 (most extremely ill).
Time frame: Baseline
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. n=number of subjects with a value
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Normal, not at all ill (n=136) | 2 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Borderline mentally ill (n=136) | 4 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Mildly ill (n=136) | 72 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Moderately ill (n=136) | 54 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Markedly ill (n=136) | 4 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Severely ill (n=136) | 0 Participants |
| Donepezil | Clinical Global Impressions Severity (CGI-S) | Among the most extremely ill patients (n=136) | 0 Participants |
Secondary
Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS)
Scale measures subject's clinical condition at baseline for severity (CGI-S) & for improvement from baseline (CGI-I). At baseline subject rated on numerical scale, 1 (not at all ill) to 7 (most extremely ill). At follow up subject rated on 7 point Likert scale from 1(very much improved) to 7(very much worse) & 4 indicates no change from baseline
Time frame: Baseline, week 24
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. Subjects with Baseline = 136; week 24 n = 116; week 24 LOCF n = 136
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS) | Baseline (n=136) | 3.40 Score on a scale | Standard Deviation 0.67 |
| Donepezil | Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS) | Week 24 (n=116) | 3.32 Score on a scale | Standard Deviation 1.21 |
| Donepezil | Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS) | Week 24 LOCF (n=136) | 3.40 Score on a scale | Standard Deviation 1.19 |
Secondary
CLOX Differential Score Change From Baseline; Full Analysis Set (FAS)
CLOX differential score equals the difference between the score for CLOX 2 and the score for CLOX 1, values range from 15 to 0, with 0 indicating perfect executive function, and a worsening with the increasing score.
Time frame: Baseline, 12 weeks, 24 weeks
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward.LOCF N=131; weeks 12, 24 n = 117, 106
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | CLOX Differential Score Change From Baseline; Full Analysis Set (FAS) | week 12 (n=117) | 0.26 Score on a scale | Standard Deviation 3.5 |
| Donepezil | CLOX Differential Score Change From Baseline; Full Analysis Set (FAS) | week 24 (n=106) | -0.35 Score on a scale | Standard Deviation 3.31 |
| Donepezil | CLOX Differential Score Change From Baseline; Full Analysis Set (FAS) | week 24 LOCF (n=131) | -0.44 Score on a scale | Standard Deviation 3.36 |
p-value: 0.51695% CI: [-0.44, 0.86]Mixed Models Analysis
p-value: 0.29795% CI: [-0.97, 0.3]Mixed Models Analysis
p-value: 0.133Mixed Models Analysis
Secondary
Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS)
The ability to copy a drawing of a clock. Scored on a scale from 1 to 15; lower scores indicate higher impairment. Change: Mean CLOX 2 score at observation minus mean CLOX 2 score at baseline.
Time frame: Baseline, 12 weeks, 24 weeks
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. LOCF N=131; weeks 12, 24 n = 117, 106
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS) | week 12 (n=117) | 0.28 Score on scale | Standard Deviation 3.35 |
| Donepezil | Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS) | week 24 (n=106) | 0.84 Score on scale | Standard Deviation 2.92 |
| Donepezil | Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS) | week 24 LOCF (n=131) | 0.51 Score on scale | Standard Deviation 3.09 |
p-value: 0.36895% CI: [-0.38, 1.01]Mixed Models Analysis
p-value: 0.0395% CI: [0.07, 1.37]Mixed Models Analysis
p-value: 0.06Mixed Models Analysis
Secondary
Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain.
The ADL domain includes 17 yes/no questions on four items (hygiene, dressing, continence, eating). Score equals number of questions answered yes multiplied by 100 divided by number of questions answered. Change: Mean ADL score at observation minus mean ADL score at baseline.
Time frame: Baseline, week 12, week 24
Population: Full Analysis Set (FAS): all subjects who received at least one dose of donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward.N=137; Weeks 12, 24 n= 124, 114.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain. | week 12 (n=124) | 1.68 score on a scale | Standard Deviation 13.23 |
| Donepezil | Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain. | week 24 (n=114) | -1.61 score on a scale | Standard Deviation 19.68 |
| Donepezil | Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain. | week 24 LOCF (n=137) | -1.88 score on a scale | Standard Deviation 18.15 |
p-value: 0.21895% CI: [-1.2, 5.19]Mixed Models Analysis
p-value: 0.38595% CI: [-6.03, 2.34]Mixed Models Analysis
p-value: 0.228Mixed Models Analysis
Secondary
Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain.
IADL domain consists of 23 yes-no questions on 6 items (meal preparation, telephoning, going out, finance & correspondence, medications, leisure & housework. Change: Mean IADL score at observation minus mean IADL score at baseline. Total IADL score = number of questions answered yes multiplied by 100 divided by total number of questions answered
Time frame: Baseline, 12 weeks, 24 weeks
Population: Full Analysis Set (FAS):all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward.N=137; Weeks 12, 24 n= 124,114
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain. | week 12 (n=124) | 1.68 score on a scale | Standard Deviation 18.01 |
| Donepezil | Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain. | week 24 (n=114) | 0.20 score on a scale | Standard Deviation 22.37 |
| Donepezil | Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain. | week 24 LOCF (n=137) | 1.31 score on a scale | Standard Deviation 22.3 |
p-value: 0.494Mixed Models Analysis
p-value: 0.40495% CI: [-2.51, 6.18]Mixed Models Analysis
p-value: 0.82695% CI: [-4.51, 5.64]Mixed Models Analysis
Secondary
Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS)
DAD total score equals total number of questions answered yes multiplied by 100 divided by total number of questions answered.
Time frame: Baseline, week 12, week 24
Population: Full Analysis Set (FAS):all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward.N=137; Weeks 12, 24 n = 124, 114
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS) | week 12 (n=124) | 1.71 score on a scale | Standard Deviation 13.18 |
| Donepezil | Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS) | week 24 (n=114) | -0.12 score on a scale | Standard Deviation 18.01 |
| Donepezil | Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS) | week 24 LOCF (n=137) | 0.17 score on a scale | Standard Deviation 17.01 |
p-value: 0.27295% CI: [-1.42, 4.99]Mixed Models Analysis
p-value: 0.89495% CI: [-4.21, 3.68]Mixed Models Analysis
p-value: 0.906Mixed Models Analysis
Secondary
Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS)
The ability to draw a clock free-hand. Scored on a scale from 1 to 15; lower scores indicate higher impairment. Change: Mean CLOX 1 score at observation minus mean CLOX score at baseline.
Time frame: Baseline, 12 weeks, 24 weeks
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. N=137; weeks 12, 24 n = 123, 111
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS) | Week 12 (n=123) | -0.03 Score on a scale | Standard Deviation 3.08 |
| Donepezil | Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS) | Week 24 (n=111) | 0.95 Score on a scale | Standard Deviation 3.13 |
| Donepezil | Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS) | Week LOCF (n=137) | 0.74 Score on a scale | Standard Deviation 3.13 |
p-value: 0.71995% CI: [-0.56, 0.82]Mixed Models Analysis
p-value: 0.00695% CI: [0.29, 1.71]Mixed Models Analysis
p-value: 0.007Mixed Models Analysis
Secondary
Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS)
The total NPI-Q-D score is equal to the sum of all indiviudal symptom distress scale scores with a range of 0 to 60
Time frame: Baseline, week 12, week 24
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward.LOCF n=137; weeks 12, 24 n = 124, 114
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS) | week 12 (n=124) | -0.95 Score on a scale | Standard Deviation 5.54 |
| Donepezil | Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS) | week 24 (n=114) | -1.37 Score on a scale | Standard Deviation 6.25 |
| Donepezil | Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS) | week 24 LOCF (n=137) | -1.08 Score on a scale | Standard Deviation 6.04 |
p-value: 0.18295% CI: [-2.06, 0.39]Mixed Models Analysis
p-value: 0.11495% CI: [-2.44, 0.26]Mixed Models Analysis
p-value: 0.038Mixed Models Analysis
Secondary
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS)
NPI-Q measures severity of behavioural manifestations of dementia & the level of distress each symptom gives the main caregiver, 1 (mild), 3 (severe), 0 if symptom absent, NPI-Q also measures the caregiver distress associated with each symptom,0(no distress)to 5(very severe), total score equals sum of individual item scores & ranges from 0 to 36
Time frame: Baseline, 12 weeks, 24 weeks
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. LOCF n=137; weeks 12, 24 n = 124, 114
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS) | week 12 (n=124) | -1.06 Score on scale | Standard Deviation 4.02 |
| Donepezil | Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS) | week 24 (n=114) | -1.20 Score on scale | Standard Deviation 4.19 |
| Donepezil | Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS) | week 24 LOCF (n=137) | -1.19 Score on scale | Standard Deviation 4.03 |
p-value: 0.0195% CI: [-1.93, -0.27]Mixed Models Analysis
p-value: 0.01895% CI: [-2.05, -0.19]Mixed Models Analysis
p-value: 0.018Mixed Models Analysis
Secondary
Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS)
The number of words a particpant can generate in 1 minute.
Time frame: Baseline, 12 weeks, week 24
Population: Full Analysis Set (FAS): all subjects who received at least one dose donepezil and who have baseline and at least one post-baseline assessment of efficacy and LOCF = Last Observation Carried Forward. LOCF n=136; weeks 12, 24 n = 123, 113
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil | Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS) | week 12 (n=123) | 0.84 score on scale | Standard Deviation 2.85 |
| Donepezil | Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS) | week 24 (n=113) | 0.92 score on scale | Standard Deviation 3.38 |
| Donepezil | Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS) | week 24 LOCF (n=136) | 0.83 score on scale | Standard Deviation 3.29 |
p-value: 0.0295% CI: [0.13, 1.45]Mixed Models Analysis
p-value: 0.01895% CI: [0.16, 1.59]Mixed Models Analysis
p-value: 0.004Mixed Models Analysis