Vaspect Study - An Open-Label Trial Of Donepezil in Vascular and Mixed Dementia - Study Results

Study Type:	Interventional
Study Design:	Non-Randomized, Open Label, Single Group Assignment
Conditions:	Dementia, Vascular Dementia, Mixed
Intervention:	Drug: Donepezil

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study was conducted in Canada in 30 centres.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

	Donepezil
STARTED	149^[1]
COMPLETED	116
NOT COMPLETED	33
Death	2
Adverse Event	19
Withdrawal by Subject	6
Protocol Violation	3
Arrived early for last visit in error	1
Subject felt pill not effective enough	1
Lost to Follow-up	1

[1]	148 are summarized below: 1 subject entered the study but was lost to follow up.

	Donepezil
Number of Participants [units: participants]	149
Age, Customized [units: Participants]
< 45	0
45-64	20
>= 65	129
Gender [units: participants]
Female	82
Male	67

Measure Type	Primary
Measure Title	Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set [units: Score on a scale] Mean ± Standard Deviation
Week 12 (n=124)	0.41 ± 3.10
Week 24 (n=114)	0.69 ± 3.2
Week 24 LOCF (n=137)	0.48 ± 3.25

Statistical Analysis 1 for Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.182
Mean Difference (Net) ^[4]	0.44
Standard Error of the mean	± 0.33
95% Confidence Interval	( -0.21 to 1.09 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Baseline value, center, and week as fixed effects; subject was included as a random effect.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.067
Mean Difference (Net) ^[4]	0.66
Standard Error of the mean	± 0.36
95% Confidence Interval	( -0.05 to 1.36 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Change in Total Score of Standardized Mini-Mental State Examination (sMMSE); Full Analysis Set

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.085

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	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.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain.
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain. [units: score on a scale] Mean ± Standard Deviation
week 12 (n=124)	1.68 ± 13.23
week 24 (n=114)	-1.61 ± 19.68
week 24 LOCF (n=137)	-1.88 ± 18.15

Statistical Analysis 1 for Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.218
Mean Difference (Net) ^[4]	2.0
Standard Error of the mean	± 1.16
95% Confidence Interval	( -1.20 to 5.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.385
Median Difference (Net) ^[4]	-1.85
Standard Error of the mean	± 2.12
95% Confidence Interval	( -6.03 to 2.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Disability Assessment for Dementia Change From Baseline; Activities of Daily Living (ADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.228

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain.
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain. [units: score on a scale] Mean ± Standard Deviation
week 12 (n=124)	1.68 ± 18.01
week 24 (n=114)	0.20 ± 22.37
week 24 LOCF (n=137)	1.31 ± 22.30

Statistical Analysis 1 for Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.404
Mean Difference (Net) ^[4]	1.84
Standard Error of the mean	± 2.19
95% Confidence Interval	( -2.51 to 6.18 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.826
Mean Difference (Net) ^[4]	0.57
Standard Error of the mean	± 2.56
95% Confidence Interval	( -4.51 to 5.64 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Disability Assessment for Dementia Change From Baseline; Instrumental ADL (IADL) Domain.

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.494

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS) [units: score on a scale] Mean ± Standard Deviation
week 12 (n=124)	1.71 ± 13.18
week 24 (n=114)	-0.12 ± 18.01
week 24 LOCF (n=137)	0.17 ± 17.01

Statistical Analysis 1 for Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.272
Mean Difference (Net) ^[4]	1.78
Standard Error of the mean	± 1.61
95% Confidence Interval	( -1.42 to 4.99 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.894
Mean Difference (Net) ^[4]	-0.27
Standard Error of the mean	± 2.00
95% Confidence Interval	( -4.21 to 3.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Disability Assessment for Dementia (DAD) Change From Baseline Total Score; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.906

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS) [units: Score on a scale] Mean ± Standard Deviation
Week 12 (n=123)	-0.03 ± 3.08
Week 24 (n=111)	0.95 ± 3.13
Week LOCF (n=137)	0.74 ± 3.13

Statistical Analysis 1 for Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.719
Mean Difference (Net) ^[4]	0.13
Standard Error of the mean	± 0.35
95% Confidence Interval	( -0.56 to 0.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.006
Median Difference (Net) ^[4]	1.00
Standard Error of the mean	± 0.36
95% Confidence Interval	( 0.29 to 1.71 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Free-hand Drawing Test (CLOX 1) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.007

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	131
Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS) [units: Score on scale] Mean ± Standard Deviation
week 12 (n=117)	0.28 ± 3.35
week 24 (n=106)	0.84 ± 2.92
week 24 LOCF (n=131)	0.51 ± 3.09

Statistical Analysis 1 for Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.368
Mean Difference (Net) ^[4]	0.32
Standard Error of the mean	± 0.35
95% Confidence Interval	( -0.38 to 1.01 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.030
Mean Difference (Net) ^[4]	0.72
Standard Error of the mean	± 0.33
95% Confidence Interval	( 0.07 to 1.37 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Copied Clock Drawing Test (CLOX 2) Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.060

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	CLOX Differential Score Change From Baseline; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	131
CLOX Differential Score Change From Baseline; Full Analysis Set (FAS) [units: Score on a scale] Mean ± Standard Deviation
week 12 (n=117)	0.26 ± 3.50
week 24 (n=106)	-0.35 ± 3.31
week 24 LOCF (n=131)	-0.44 ± 3.36

Statistical Analysis 1 for CLOX Differential Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.516
Mean Difference (Net) ^[4]	0.21
Standard Error of the mean	± 0.33
95% Confidence Interval	( -0.44 to 0.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for CLOX Differential Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.297
Mean Difference (Net) ^[4]	-0.34
Standard Error of the mean	± 0.32
95% Confidence Interval	( -0.97 to 0.30 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for CLOX Differential Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.133

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS)
Measure Description	The number of words a particpant can generate in 1 minute.
Time Frame	Baseline, 12 weeks, week 24
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	136
Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS) [units: score on scale] Mean ± Standard Deviation
week 12 (n=123)	0.84 ± 2.85
week 24 (n=113)	0.92 ± 3.38
week 24 LOCF (n=136)	0.83 ± 3.29

Statistical Analysis 1 for Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.020
Median Difference (Net) ^[4]	0.79
Standard Error of the mean	± 0.33
95% Confidence Interval	( 0.13 to 1.45 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.018
Median Difference (Net) ^[4]	0.87
Standard Error of the mean	± 0.36
95% Confidence Interval	( 0.16 to 1.59 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Phonectic Fluency Total Score From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.004

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS) [units: Score on scale] Mean ± Standard Deviation
week 12 (n=124)	-1.06 ± 4.02
week 24 (n=114)	-1.20 ± 4.19
week 24 LOCF (n=137)	-1.19 ± 4.03

Statistical Analysis 1 for Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.010
Mean Difference (Net) ^[4]	-1.10
Standard Error of the mean	± 0.42
95% Confidence Interval	( -1.93 to -0.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.018
Mean Difference (Net) ^[4]	-1.12
Standard Error of the mean	± 0.47
95% Confidence Interval	( -2.05 to -0.19 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Neuropsychiatric Inventory Questionnaire (NPI-Q) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.018

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	137
Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS) [units: Score on a scale] Mean ± Standard Deviation
week 12 (n=124)	-0.95 ± 5.54
week 24 (n=114)	-1.37 ± 6.25
week 24 LOCF (n=137)	-1.08 ± 6.04

Statistical Analysis 1 for Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.182
Mean Difference (Net) ^[4]	-0.83
Standard Error of the mean	± 0.62
95% Confidence Interval	( -2.06 to 0.39 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.114
Mean Difference (Net) ^[4]	-1.09
Standard Error of the mean	± 0.68
95% Confidence Interval	( -2.44 to 0.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Neuropsychiatric Inventory Questionnaire Distress (NPI-Q-D) Score Change From Baseline; Full Analysis Set (FAS)

Groups ^[1]	Donepezil
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.038

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Measure Type	Secondary
Measure Title	Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	136
Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS) [units: Score on a scale] Mean ± Standard Deviation
Baseline (n=136)	3.40 ± 0.67
Week 24 (n=116)	3.32 ± 1.21
Week 24 LOCF (n=136)	3.40 ± 1.19

No statistical analysis provided for Clinical Global Impressions Severity Score (CGI-S) Clinical Global Impressions Severity Score Improvement(CGI-I)Change From Baseline, Full Analysis Set (FAS)

Measure Type	Secondary
Measure Title	Clinical Global Impressions Severity (CGI-S)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	136
Clinical Global Impressions Severity (CGI-S) [units: Participants]
Normal, not at all ill (n=136)	2
Borderline mentally ill (n=136)	4
Mildly ill (n=136)	72
Moderately ill (n=136)	54
Markedly ill (n=136)	4
Severely ill (n=136)	0
Among the most extremely ill patients (n=136)	0

No statistical analysis provided for Clinical Global Impressions Severity (CGI-S)

Measure Type	Secondary
Measure Title	Clinical Global Impressions Improvement (CGI-I)
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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)

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	136
Clinical Global Impressions Improvement (CGI-I) [units: Participants]
Wk 24 Very much improved (n=116)	3
Wk 24 Much improved (n=116)	27
Wk 24 Minimally improved (n=116)	44
Wk 24 No change (n=116)	21
Wk 24 Minimally worse (n=116)	14
Wk 24 Much worse (n=116)	7
Wk 24 Very much worse (n=116)	0
Wk 24 LOCF Very much improved (n=136)	4
Wk 24 LOCF Much improved (n=136)	27
Wk 24 LOCF Minimally improved (n=136)	49
Wk 24 LOCF No change (n=136)	30
Wk 24 LOCF Minimally worse (n=136)	19
Wk 24 LOCF Much worse (n=136)	7
Wk 24 LOCF Very much worse (n=136)	0

No statistical analysis provided for Clinical Global Impressions Improvement (CGI-I)

Measure Type	Secondary
Measure Title	Clinical Global Impressions Improvement (CGI-I) Dichotomized Response
Measure Description	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
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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

Reporting Groups

	Description
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.

Measured Values

	Donepezil
Number of Participants Analyzed [units: participants]	136
Clinical Global Impressions Improvement (CGI-I) Dichotomized Response [units: Particpants]
Week 24 Responder (n=116)	95
Week 24 Non-responder (n=116)	21
Week 24 LOCF Responder (n=136)	110
Week 24 LOCF Non-responder (n=136)	26

No statistical analysis provided for Clinical Global Impressions Improvement (CGI-I) Dichotomized Response

Responsible Party:	Pfizer, Inc. ( Director, Clinical Trials Disclosure Group )
Study ID Numbers:	A2501026
Study First Received:	September 8, 2005
Results First Received:	April 24, 2009
Last Updated:	July 20, 2009
ClinicalTrials.gov Identifier:	NCT00174382 History of Changes
Health Authority:	Canada: Health Canada