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Trial record 7 of 31 for:    alzheimer dijon

A Long-Term Safety And Tolerability Extension Study Of Bapineuzumab In Alzheimer Disease Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00998764
Recruitment Status : Terminated (The study was terminated on August 6, 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns.)
First Posted : October 20, 2009
Results First Posted : January 1, 2016
Last Update Posted : January 1, 2016
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Intervention: Drug: Bapineuzumab 0.5 mg/kg

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted at 147 centers in 19 countries. The study was terminated early by the sponsor on 06 August 2012. Subjects who had not completed the final follow-up visit prior to 06 August 2012 were asked to complete an early termination visit.

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

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by intravenous (IV) infusion approximately every 13 weeks up to week 195.
Bapineuzumab/Bapineuzumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Participant Flow:   Overall Study
    Placebo/Bapineuzumab   Bapineuzumab/Bapineuzumab
STARTED   216   276 
Treated   215   275 
COMPLETED   0   2 
NOT COMPLETED   216   274 
Lack of Efficacy                3                6 
Adverse Event                17                12 
Withdrawal by Subject                19                25 
Physician Decision                3                3 
Death                3                1 
Discontinuation of Study by Sponsor                164                217 
Protocol Violation                0                1 
Failed to Return                1                1 
Lost to Follow-up                1                1 
Loss of Caregiver                0                3 
Not specified                4                4 
Recurrent Episode of vasogenic edema                1                0 



  Baseline Characteristics

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.
The safety population included all participants who consented to participate in the extension and received at least one dose of the investigational product (in the extension study).

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study Bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapineuzumab/Bapineuzumab Participants received Bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Total Total of all reporting groups

Baseline Measures
   Placebo/Bapineuzumab   Bapineuzumab/Bapineuzumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 215   275   490 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.4  (8.14)   72.1  (7.47)   71.8  (7.77) 
Age, Customized 
[Units: Participants]
     
< 65 years   44   42   86 
>= 65 years   171   233   404 
Gender 
[Units: Participants]
     
Female   135   186   321 
Male   80   89   169 


  Outcome Measures

1.  Primary:   Number of Participants Reporting a Serious Adverse Event   [ Time Frame: Up to Week 195 ]

Measure Type Primary
Measure Title Number of Participants Reporting a Serious Adverse Event
Measure Description Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.
Time Frame Up to Week 195  

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.
Safety population

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapineuzumab/Bapineuzumab Participants received bapineuzumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapineuzumab/Bapineuzumab 
Participants Analyzed   215   275 
Number of Participants Reporting a Serious Adverse Event 
[Units: Number of Participants]
 35   33 

No statistical analysis provided for Number of Participants Reporting a Serious Adverse Event



2.  Secondary:   Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78   [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Measure Description The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8 remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
Time Frame Base Study Baseline, Weeks 13, 26, 39, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapineuzumab/Bapineuzumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapineuzumab/Bapineuzumab 
Participants Analyzed   199   256 
Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 13 (N= 197, 253)   5.53  (0.57)   6.28  (0.50) 
Week 26 (N = 154, 221)   7.41  (0.63)   7.70  (0.54) 
Week 39 (N = 121, 184)   8.83  (0.72)   8.87  (0.61) 
Week 52 (N = 91, 139)   10.12  (0.75)   10.11  (0.63) 
Week 78 (N = 52, 80)   13.91  (0.96)   12.70  (0.80) 


Statistical Analysis 1 for Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.324
Mean Difference (Final Values) [5] 0.74
95% Confidence Interval -0.74 to 2.23
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 13
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.723
Mean Difference (Final Values) [5] 0.29
95% Confidence Interval -1.33 to 1.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 26
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.966
Mean Difference (Final Values) [5] 0.04
95% Confidence Interval -1.81 to 1.89
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 39
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.996
Mean Difference (Final Values) [5] 0.00
95% Confidence Interval -1.93 to 1.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 52
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.336
Mean Difference (Final Values) [5] -1.21
95% Confidence Interval -3.67 to 1.26
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog) at week 78
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



3.  Secondary:   Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Measure Description The ADAS-Cog is a multi-item, objective measure of cognitive function. The scale evaluates memory, language, and praxis with items such as orientation, word recall, word recognition, object identification, comprehension, and the completion of simple tasks. Analysis of the ADAS-Cog for this study was based upon an 11 item score from the following items 1) word recall task, 2) naming objects and fingers, 3) following commands, 4)constructional praxis, 5) ideational praxis, 6) orientation, 7) word recognition, 8)remembering test instructions, 9) spoken language ability, 10) word finding difficulty in spontaneous speech, and 11) comprehension.This scale had to be administered by a trained and certified psychometric rater who did not have access to any information regarding adverse events experienced. The ADAS-Cog/11 ranged from 0 to 70 points, with higher scores indicating a greater degree of impairment. A negative change from baseline indicates a decrease in cognitive impairment.
Time Frame Base Study Baseline, Weeks 13, 26, 39, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapineuzumab/Bapineuzumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapineuzumab/Bapineuzumab 
Participants Analyzed   199   256 
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 13 (N = 197, 253)   0.89  (0.36)   0.73  (0.32) 
Week 26 (N = 154, 221)   2.87  (0.42)   2.19  (0.35) 
Week 39 (N = 121, 184)   4.26  (0.50)   3.35  (0.42) 
Week 52 (N = 91, 139)   5.42  (0.55)   4.51  (0.45) 
Week 78 (N = 52, 80)   9.21  (0.82)   7.07  (0.66) 


Statistical Analysis 1 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.737
Mean Difference (Final Values) [5] -0.16
95% Confidence Interval -1.11 to 0.79
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in ADAS-Cog at week 13
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.213
Mean Difference (Final Values) [5] -0.68
95% Confidence Interval -1.76 to 0.40
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in ADAS-Cog at week 26
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.168
Mean Difference (Final Values) [5] -0.90
95% Confidence Interval -2.19 to 0.38
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in ADAS-Cog at week 39
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.197
Mean Difference (Final Values) [5] -0.91
95% Confidence Interval -2.30 to 0.48
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in ADAS-Cog at week 52
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.044
Mean Difference (Final Values) [5] -2.13
95% Confidence Interval -4.21 to 0.06
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in ADAS-Cog at week 78
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



4.  Secondary:   Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Measure Description The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant’s caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is “yes” and a zero score was assigned if the answer is “no”. For questions answered as “not applicable”, no score will be assigned. The DAD total score was calculated as the total number of questions answered as “yes” divided by the total number of questions answered as “yes” or “no”, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 13, 26, 39, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 13 (N = 194, 247)   -12.33  (1.27)   15.32  (1.11) 
Week 26 (N = 151, 222)   -15.37  (1.29)   -18.04  (1.11) 
Week 39 (N = 119, 180)   -17.74  (1.47)   -21.33  (1.24) 
Week 52 (N = 89, 137)   -20.96  (1.65)   -22.72  (1.36) 
Week 78 (N = 50, 81)   -26.33  (2.18)   -29.11  (1.75) 


Statistical Analysis 1 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.077
Mean Difference (Final Values) [5] -2.99
95% Confidence Interval -6.30 to 0.33
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in DAD score at Week 13
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.117
Mean Difference (Final Values) [5] -2.67
95% Confidence Interval -6.02 to 0.67
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in DAD score at Week 26
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.063
Mean Difference (Final Values) [5] -3.60
95% Confidence Interval -7.38 to 0.19
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in DAD score at Week 39
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.412
Mean Difference (Final Values) [5] -1.75
95% Confidence Interval -5.95 to 2.44
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in DAD score at Week 52
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.321
Mean Difference (Final Values) [5] -2.78
95% Confidence Interval -8.28 to 2.73
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in DAD score at Week 78
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



5.  Secondary:   Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: Base Study Baseline, Weeks 13, 26, 39, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Measure Description The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant’s caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is “yes” and a zero score was assigned if the answer is “no”. For questions answered as “not applicable”, no score will be assigned. The DAD total score was calculated as the total number of questions answered as “yes” divided by the total number of questions answered as “yes” or “no”, times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 13, 26, 39, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. 
[Units: Units on scale]
Least Squares Mean (Standard Error)
   
Week 13 (N = 194, 247)   -2.63  (0.83)   -3.71  (0.73) 
Week 26 (N = 151, 222)   -5.76  (1.01)   -6.46  (0.86) 
Week 39 (N = 119, 180)   -8.17  (1.22)   -9.72  (1.02) 
Week 52 (N = 89, 137)   -11.82  (1.34)   -11.11  (1.10) 
Week 78 (N = 50, 81)   -17.34  (1.94)   -17.48  (1.56) 


Statistical Analysis 1 for Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.329
Mean Difference (Final Values) [5] -1.08
95% Confidence Interval -3.24 to 1.09
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in DAD score at Week 13
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.601
Mean Difference (Final Values) [5] -0.70
95% Confidence Interval -3.31 to 1.92
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in DAD score at Week 26
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.328
Mean Difference (Final Values) [5] -1.55
95% Confidence Interval -4.67 to 1.56
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in DAD score at Week 39
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.680
Mean Difference (Final Values) [5] 0.71
95% Confidence Interval -2.70 to 4.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in DAD score at Week 52
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.954
Mean Difference (Final Values) [5] -0.14
95% Confidence Interval -5.05 to 4.77
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in DAD score at Week 78
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



6.  Secondary:   Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.   [ Time Frame: Base Study Baseline, Weeks 26, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Measure Description NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 26, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 26 (N = 176, 240)   2.84  (0.97)   2.95  (0.83) 
Week 52 (N = 110, 163)   4.32  (0.96)   3.52  (0.80) 
Week 78 (N = 51, 81)   6.95  (1.70)   4.93  (1.36) 


Statistical Analysis 1 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.931
Mean Difference (Final Values) [5] 0.11
95% Confidence Interval -2.40 to 2.62
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in NPI score at week 26.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.524
Mean Difference (Final Values) [5] -0.80
95% Confidence Interval -3.26 to 1.67
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in NPI score at week 52.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.353
Mean Difference (Final Values) [5] -2.03
95% Confidence Interval -6.32 to 2.27
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in NPI score at week 78.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



7.  Secondary:   Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.   [ Time Frame: Base Study Baseline, Weeks 26, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Measure Description NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 26, 52 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 26 (N = 176, 240)   2.17  (0.86)   1.47  (0.73) 
Week 52 (N = 110, 163)   3.82  (0.95)   1.98  (0.79) 
Week 78 (N = 51, 81)   6.60  (1.69)   3.29  (1.35) 


Statistical Analysis 1 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.531
Mean Difference (Final Values) [5] -0.71
95% Confidence Interval -2.92 to 1.51
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in NPI score at week 26.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.137
Mean Difference (Final Values) [5] -1.84
95% Confidence Interval -4.28 to 0.59
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in NPI score at week 52.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.128
Mean Difference (Final Values) [5] -3.32
95% Confidence Interval -7.60 to 0.96
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in NPI score at week 78.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



8.  Secondary:   Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78 ]

Measure Type Secondary
Measure Title Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Measure Description MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 6, 19, 32, 45 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 6 (N= 197, 255)   -2.61  (0.22)   -2.55  (0.19) 
Week 19 (N = 184, 241)   -3.13  (0.22)   -3.01  (0.19) 
Week 32 (N = 141, 204)   -3.75  (0.24)   -3.65  (0.20) 
Week 45 (N = 117, 171)   -4.44  (0.26)   -4.26  (0.21) 
Week 78 (N = 65, 94)   -5.50  (0.32)   -5.54  (0.26) 


Statistical Analysis 1 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.811
Mean Difference (Final Values) [5] 0.07
95% Confidence Interval -0.49 to 0.63
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in MMSE score at Week 6.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.681
Mean Difference (Final Values) [5] 0.12
95% Confidence Interval -0.45 to 0.69
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from base study baseline in MMSE score at Week 19.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.742
Mean Difference (Final Values) [5] 0.10
95% Confidence Interval -0.51 to 0.72
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 32.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.598
Mean Difference (Final Values) [5] 0.18
95% Confidence Interval -0.48 to 0.83
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 45.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.922
Mean Difference (Final Values) [5] -0.04
95% Confidence Interval -0.85 to 0.77
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 78.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.



9.  Secondary:   Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: Base Study Baseline, Weeks 6, 19, 32, 45 and 78 ]

Measure Type Secondary
Measure Title Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Measure Description MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.
Time Frame Base Study Baseline, Weeks 6, 19, 32, 45 and 78  

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.
The Modified Intent-to-Treat (mITT) Population was defined as all randomly assigned participants who received investigational product in the base study, had a baseline for the base study, had at least one valid post-baseline assessment of the ADAS-Cog and DAD total score in the base study and signed informed consent in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Bapinezumab/Bapinezumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.

Measured Values
   Placebo/Bapineuzumab   Bapinezumab/Bapinezumab 
Participants Analyzed   199   256 
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. 
[Units: Units on a scale]
Least Squares Mean (Standard Error)
   
Week 6 (N = 195, 255)   -0.67  (0.19)   -0.26  (0.16) 
Week 19 (N = 182, 241)   -1.16  (0.21)   -0.69  (0.18) 
Week 32 (N = 140, 204)   -1.85  (0.24)   -1.40  (0.20) 
Week 45 (N = 116, 171)   -2.57  (0.28)   -2.05  (0.24) 
Week 78 (N = 64, 94)   -3.69  (0.39)   -3.42  (0.32) 


Statistical Analysis 1 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.099
Mean Difference (Final Values) [5] 0.41
95% Confidence Interval -0.08 to 0.90
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 6.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.089
Mean Difference (Final Values) [5] 0.47
95% Confidence Interval -0.07 to 1.01
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 19.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.152
Mean Difference (Final Values) [5] 0.45
95% Confidence Interval -0.17 to 1.08
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 32.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
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[3] Other relevant method information, such as adjustments or degrees of freedom:
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[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[5] Other relevant estimation information:
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Statistical Analysis 4 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.160
Mean Difference (Final Values) [5] 0.52
95% Confidence Interval -0.21 to 1.25
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 45.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
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[3] Other relevant method information, such as adjustments or degrees of freedom:
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[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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[5] Other relevant estimation information:
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Statistical Analysis 5 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] Mixed Models Analysis
P Value [4] 0.603
Mean Difference (Final Values) [5] 0.26
95% Confidence Interval -0.73 to 1.26
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Change from extension study baseline in MMSE score at Week 78.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[4] 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.
[5] Other relevant estimation information:
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  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00998764     History of Changes
Other Study ID Numbers: 3133K1-3003
B2521004 ( Other Identifier: Alias Study Number )
2009-015080-13 ( EudraCT Number )
First Submitted: October 16, 2009
First Posted: October 20, 2009
Results First Submitted: October 15, 2013
Results First Posted: January 1, 2016
Last Update Posted: January 1, 2016