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

This study has been 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.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00996918
First received: October 14, 2009
Last updated: November 12, 2013
Last verified: November 2013
Results First Received: November 12, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer Disease
Interventions: Drug: Bapineuzumab 0.5 mg/kg
Drug: Bapineuzumab 1.0 m/kg

  Participant Flow
  Hide 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 extension study was conducted at 91 centers in 17 countries. The study was terminated early by the sponsor on 06 August 2012. Participants 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
Participants who had completed the base study protocol 3133K1-3000 were allowed to participate in this extension study. Participants who developed vasogenic edema during study 3133K1-3000 were considered for study 3133K1-3002 participation if the abnormality was resolved and the participant met criteria to resume the investigational product.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 Milligram/Kilogram(mg/kg) Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Participant Flow:   Overall Study
    Placebo/Bapineuzumab 0.5 Milligram/Kilogram(mg/kg)     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg     Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg  
STARTED     39     66     37     56     4  
Treated     39     66     37     56     4  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     39     66     37     56     4  
Lack of Efficacy                 1                 1                 2                 2                 0  
Adverse Event                 2                 5                 2                 6                 0  
Withdrawal by Subject                 1                 4                 3                 3                 2  
Physician Decision                 1                 0                 0                 0                 0  
Discontinuation of Study by Sponsor                 31                 54                 30                 45                 2  
Loss of Caregiver                 0                 1                 0                 0                 0  
Not Specified                 3                 1                 0                 0                 0  



  Baseline Characteristics
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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.
No text entered.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Total Total of all reporting groups

Baseline Measures
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg     Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg     Total  
Number of Participants  
[units: participants]
  38     62     33     53     4     190  
Age  
[units: Years]
Mean ± Standard Deviation
  68.9  ± 9.70     71.9  ± 8.83     68.8  ± 8.59     70.6  ± 9.13     71.3  ± 10.63     70.4  ± 9.08  
Age, Customized  
[units: Number of participants]
           
< 65     17     15     12     17     1     62  
>= 65     21     47     21     36     3     128  
Gender  
[units: Number of participants]
           
Female     13     28     14     19     3     77  
Male     25     34     19     34     1     113  



  Outcome Measures
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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  
Safety Issue Yes  

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 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg     Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  39     66     37     56     4  
Number of Participants Reporting a Serious Adverse Event.  
[units: Number of participants]
  6     10     1     11     0  

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: 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 Weeks 13, 26, 39, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 38, 62, 33, 53)     7.47  ± 1.17     6.17  ± 0.95     4.66  ± 1.26     6.45  ± 0.98  
Week 26 (N = 33, 54, 26, 45)     9.00  ± 1.27     7.49  ± 1.03     7.34  ± 1.38     7.30  ± 1.07  
Week 39 (N = 25, 46, 22, 37)     9.74  ± 1.35     8.79  ± 1.08     7.92  ± 1.45     9.50  ± 1.12  
Week 52 (N = 18, 32, 15, 29)     12.44  ± 1.70     10.38  ± 1.35     10.54  ± 1.82     10.31  ± 1.36  
Week 78 (N = 12, 19, 8, 20)     14.71  ± 2.12     12.27  ± 1.81     15.46  ± 2.46     15.31  ± 1.68  


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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.390
Mean Difference (Final Values) [4] -1.30
95% Confidence Interval ( -4.29 to 1.68 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 13.

Results are from a restricted maximum likelihood (REML)-based mixed model for repeated measures (MMRM) with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.264
Mean Difference (Final Values) [4] 1.80
95% Confidence Interval ( -1.37 to 4.97 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 13.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.357
Mean Difference (Final Values) [4] -1.51
95% Confidence Interval ( -4.74 to 1.72 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.981
Mean Difference (Final Values) [4] -0.04
95% Confidence Interval ( -3.50 to 3.42 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.584
Mean Difference (Final Values) [4] -0.95
95% Confidence Interval ( -4.37 to 2.47 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 39.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 6 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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.392
Mean Difference (Final Values) [4] 1.58
95% Confidence Interval ( -2.05 to 5.20 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 39.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 7 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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.345
Mean Difference (Final Values) [4] -2.05
95% Confidence Interval ( -6.34 to 2.24 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 8 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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.922
Mean Difference (Final Values) [4] -0.22
95% Confidence Interval ( -4.73 to 4.28 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 9 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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.384
Mean Difference (Final Values) [4] -2.44
95% Confidence Interval ( -7.97 to 3.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 10 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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.961
Mean Difference (Final Values) [4] -0.15
95% Confidence Interval ( -6.08 to 5.78 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in ADAS-Cog score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



3.  Secondary:   Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: 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 Weeks 13, 26, 39, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 38, 62, 33, 53)     0.10  ± 0.84     0.32  ± 0.68     -1.68  ± 0.90     0.46  ± 0.70  
Week 26 (N = 33, 54, 26, 45)     1.61  ± 0.92     1.63  ± 0.75     1.08  ± 1.01     1.37  ± 0.78  
Week 39 (N = 25, 46, 22, 37)     2.35  ± 1.01     2.86  ± 0.79     1.68  ± 1.07     3.62  ± 0.83  
Week 52 (N = 18, 32, 15, 29)     4.85  ± 1.45     4.45  ± 1.14     4.30  ± 1.55     4.43  ± 1.14  
Week 78 (N = 12, 19, 8, 20)     7.29  ± 1.81     6.73  ± 1.57     8.86  ± 2.15     9.68  ± 1.42  


Statistical Analysis 1 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.837
Mean Difference (Final Values) [4] 0.22
95% Confidence Interval ( -1.91 to 2.35 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 13.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 2 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.064
Mean Difference (Final Values) [4] 2.14
95% Confidence Interval ( -0.13 to 4.41 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 13.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.990
Mean Difference (Final Values) [4] 0.01
95% Confidence Interval ( -2.32 to 2.35 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.817
Mean Difference (Final Values) [4] 0.30
95% Confidence Interval ( -2.22 to 2.82 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 5 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.697
Mean Difference (Final Values) [4] 0.50
95% Confidence Interval ( -2.04 to 3.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 39.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 6 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.158
Mean Difference (Final Values) [4] 1.93
95% Confidence Interval ( -0.76 to 4.63 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 39.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 7 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.829
Mean Difference (Final Values) [4] -0.40
95% Confidence Interval ( -4.06 to 3.26 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 8 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.950
Mean Difference (Final Values) [4] 0.12
95% Confidence Interval ( -3.69 to 3.93 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 9 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.816
Mean Difference (Final Values) [4] -0.56
95% Confidence Interval ( -5.35 to 4.23 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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[4] Other relevant estimation information:
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Statistical Analysis 10 for Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.751
Mean Difference (Final Values) [4] 0.82
95% Confidence Interval ( -4.32 to 5.96 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in ADAS-Cog score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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[4] Other relevant estimation information:
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4.  Secondary:   Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.   [ Time Frame: 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 participants with Alzheimer's Disease (AD). The DAD is administered to the participants’caregiver in the form of an interview. 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 by the participant. This scale assesses a participants’ ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement
Time Frame Weeks 13, 26, 39, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 38, 62, 31, 52)     -18.75  ± 2.88     -18.60  ± 2.36     -15.50  ± 3.13     -13.36  ± 2.43  
Week 26 (N = 33, 56, 26, 44)     -21.19  ± 2.93     -21.04  ± 2.38     -16.26  ± 3.19     -19.18  ± 2.48  
Week 39 (N = 25, 46, 21, 37)     -25.42  ± 3.14     -27.36  ± 2.51     -14.57  ± 3.39     -19.10  ± 2.62  
Week 52 (N = 18, 32, 15, 30)     -29.52  ± 3.48     -28.00  ± 2.77     -20.41  ± 3.74     -23.21  ± 2.80  
Week 78 (N = 12, 20, 8, 20)     -36.48  ± 4.56     -35.75  ± 3.79     -25.21  ± 5.24     -30.28  ± 3.65  


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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.967
Mean Difference (Final Values) [4] 0.16
95% Confidence Interval ( -7.22 to 7.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 13.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.593
Mean Difference (Final Values) [4] 2.13
95% Confidence Interval ( -5.72 to 9.98 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 13.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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[4] Other relevant estimation information:
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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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.968
Mean Difference (Final Values) [4] 0.15
95% Confidence Interval ( -7.32 to 7.62 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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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] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.473
Mean Difference (Final Values) [4] -2.92
95% Confidence Interval ( -10.92 to 5.08 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 5 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.630
Mean Difference (Final Values) [4] -1.95
95% Confidence Interval ( -9.91 to 6.02 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 39.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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[4] Other relevant estimation information:
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Statistical Analysis 6 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.293
Mean Difference (Final Values) [4] -4.53
95% Confidence Interval ( -13.02 to 3.95 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 39.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 7 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.733
Mean Difference (Final Values) [4] 1.53
95% Confidence Interval ( -7.28 to 10.33 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 8 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.550
Mean Difference (Final Values) [4] -2.81
95% Confidence Interval ( -12.06 to 6.45 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 9 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.902
Mean Difference (Final Values) [4] 0.73
95% Confidence Interval ( -11.04 to 12.50 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 10 for Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.430
Mean Difference (Final Values) [4] -5.07
95% Confidence Interval ( -17.75 to 7.61 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in DAD score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



5.  Secondary:   Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78   [ Time Frame: Weeks 13, 26, 39, 52 and 78 ]

Measure Type Secondary
Measure Title Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Measure Description The DAD measures instrumental and basic activities of daily living in participants with AD. The DAD is administered to the participants’caregiver in the form of an interview. 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 by the participant. This scale assesses a participants’ ability to initiate, plan, and perform activities related to hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. Each item can be scored as 1 = yes, 0 = no, non applicable = NA. A total score is obtained by adding the rating for each question and converting this total score out of 100. Higher scores indicate better function; a positive change from baseline indicates an improvement
Time Frame Weeks 13, 26, 39, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78  
[units: Units on a scale]
Least Squares Mean ± Standard Error
       
Week 13 (N = 38, 62, 31, 52)     -3.80  ± 1.96     -4.83  ± 1.60     -5.17  ± 2.16     -1.48  ± 1.65  
Week 26 (N = 33, 56, 26, 44)     -6.33  ± 2.02     -7.22  ± 1.64     -5.75  ± 2.23     -7.25  ± 1.73  
Week 39 (N = 25, 46, 21, 37)     -11.14  ± 2.23     -13.49  ± 1.76     -4.34  ± 2.41     -7.08  ± 1.85  
Week 52 (N = 18, 32, 15, 30)     -16.21  ± 2.57     -13.77  ± 2.02     -10.02  ± 2.75     -11.06  ± 2.02  
Week 78 (N = 12, 20, 8, 20)     -23.40  ± 3.01     -21.30  ± 2.54     -14.54  ± 3.54     -17.41  ± 2.37  


Statistical Analysis 1 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.683
Mean Difference (Final Values) [4] -1.03
95% Confidence Interval ( -6.01 to 3.95 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 13.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.177
Mean Difference (Final Values) [4] 3.69
95% Confidence Interval ( -1.68 to 9.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 13.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.734
Mean Difference (Final Values) [4] -0.89
95% Confidence Interval ( -6.03 to 4.25 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.595
Mean Difference (Final Values) [4] -1.50
95% Confidence Interval ( -7.06 to 4.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 5 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.409
Mean Difference (Final Values) [4] -2.35
95% Confidence Interval ( -7.95 to 3.24 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 39.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 6 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.368
Mean Difference (Final Values) [4] -2.74
95% Confidence Interval ( -8.73 to 3.24 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 39.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 7 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.458
Mean Difference (Final Values) [4] 2.44
95% Confidence Interval ( -4.01 to 8.89 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 8 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.760
Mean Difference (Final Values) [4] -1.04
95% Confidence Interval ( -7.77 to 5.68 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 9 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.597
Mean Difference (Final Values) [4] 2.09
95% Confidence Interval ( -5.67 to 9.86 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 10 for Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.501
Mean Difference (Final Values) [4] -2.87
95% Confidence Interval ( -11.24 to 5.50 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in DAD score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



6.  Secondary:   Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.   [ Time Frame: 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). Total score=sum of each domain score (range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Time Frame Weeks 26, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 36, 59, 30, 51)     4.57  ± 2.08     0.97  ± 1.70     4.71  ± 2.26     4.43  ± 1.75  
Week 52 (N = 21, 37, 17, 32)     4.99  ± 2.60     -0.01  ± 2.05     4.23  ± 2.80     6.57  ± 2.08  
Week 78 (N = 13, 18, 8, 20)     16.17  ± 3.23     3.31  ± 2.94     5.24  ± 4.02     6.70  ± 2.61  


Statistical Analysis 1 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.183
Mean Difference (Final Values) [4] -3.60
95% Confidence Interval ( -8.91 to 1.71 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.920
Mean Difference (Final Values) [4] -0.29
95% Confidence Interval ( -5.92 to 5.35 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 26.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.133
Mean Difference (Final Values) [4] -4.99
95% Confidence Interval ( -11.52 to 1.53 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.505
Mean Difference (Final Values) [4] 2.34
95% Confidence Interval ( -4.55 to 9.22 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 52.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 5 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.003
Mean Difference (Final Values) [4] -12.86
95% Confidence Interval ( -21.46 to -4.25 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 6 for Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.760
Mean Difference (Final Values) [4] 1.47
95% Confidence Interval ( -7.95 to 10.88 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in NPI score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



7.  Secondary:   Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.   [ Time Frame: 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, night-time 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). Total score=sum of each domain score(range 0-144); higher score=greater behavioral disturbances; negative change score from baseline=improvement.
Time Frame Weeks 26, 52 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 36, 60, 30, 51)     2.29  ± 1.79     0.21  ± 1.48     2.77  ± 1.96     1.73  ± 1.51  
Week 52 (N = 21, 37, 17, 32)     2.34  ± 2.45     -1.06  ± 1.94     3.78  ± 2.65     3.99  ± 1.97  
Week 78 (N = 13, 18, 8, 20)     11.76  ± 4.86     1.70  ± 4.40     2.28  ± 6.07     4.76  ± 3.93  


Statistical Analysis 1 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.373
Mean Difference (Final Values) [4] -2.08
95% Confidence Interval ( -6.68 to 2.52 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.677
Mean Difference (Final Values) [4] -1.03
95% Confidence Interval ( -5.92 to 3.86 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 26.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.280
Mean Difference (Final Values) [4] -3.40
95% Confidence Interval ( -9.61 to 2.80 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.950
Mean Difference (Final Values) [4] 0.21
95% Confidence Interval ( -6.34 to 6.76 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 52.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 5 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.130
Mean Difference (Final Values) [4] -10.06
95% Confidence Interval ( -23.16 to 3.05 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 6 for Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.732
Mean Difference (Final Values) [4] 2.48
95% Confidence Interval ( -11.97 to 16.94 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in NPI score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



8.  Secondary:   Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: 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. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state.
Time Frame Weeks 6, 19, 32, 45 and 78  
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.
The Extension mITT Population was defined as all randomly assigned participants who received at least one dose of investigational product in the extension study and who had a baseline for the extension study and at least one valid post-baseline assessment of the ADAS-Cog total score and DAD total score in the extension study.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 38, 61, 33, 53)     -2.89  ± 0.46     -2.85  ± 0.37     -2.02  ± 0.49     -2.22  ± 0.39  
Week 19 (N = 36, 59, 28, 50)     -2.80  ± 0.47     -2.66  ± 0.38     -2.76  ± 0.51     -3.29  ± 0.39  
Week 32 (N = 32, 51, 26, 41)     -3.82  ± 0.49     -3.43  ± 0.40     -4.40  ± 0.53     -3.88  ± 0.42  
Week 45 (N = 23, 41, 21, 35)     -4.86  ± 0.56     -4.13  ± 0.44     -4.63  ± 0.58     -4.51  ± 0.46  
Week 78 (N = 13, 27, 11, 21)     -7.62  ± 0.70     -5.10  ± 0.54     -6.97  ± 0.75     -4.89  ± 0.56  


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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.938
Mean Difference (Final Values) [4] 0.05
95% Confidence Interval ( -1.12 to 1.21 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 6.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.753
Mean Difference (Final Values) [4] -0.20
95% Confidence Interval ( -1.43 to 1.04 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 6.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.809
Mean Difference (Final Values) [4] 0.15
95% Confidence Interval ( -1.04 to 1.33 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 19.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.421
Mean Difference (Final Values) [4] -0.52
95% Confidence Interval ( -1.80 to 0.75 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 19.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 5 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.535
Mean Difference (Final Values) [4] 0.39
95% Confidence Interval ( -0.85 to 1.63 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 32.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 6 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.445
Mean Difference (Final Values) [4] 0.52
95% Confidence Interval ( -0.82 to 1.86 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 32.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 7 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.309
Mean Difference (Final Values) [4] 0.73
95% Confidence Interval ( -0.67 to 2.12 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 45.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 8 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.872
Mean Difference (Final Values) [4] 0.12
95% Confidence Interval ( -1.34 to 1.57 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 45.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 9 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.004
Mean Difference (Final Values) [4] 2.52
95% Confidence Interval ( 0.79 to 4.26 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 10 for Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.026
Mean Difference (Final Values) [4] 2.09
95% Confidence Interval ( 0.25 to 3.93 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from base study baseline in MMSE score at Week 78.

Results are from a REML-based MMRM with change from base study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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.



9.  Secondary:   Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.   [ Time Frame: 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. Total score derived from sub-scores; total ranged from 0 to 30, higher score indicates better cognitive state
Time Frame Weeks 6, 19, 32, 45 and 78  
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.
No text entered.

Reporting Groups
  Description
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.

Measured Values
    Placebo/Bapineuzumab 0.5 mg/kg     Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg     Placebo/Bapineuzumab 1.0 mg/kg     Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg  
Number of Participants Analyzed  
[units: participants]
  38     62     33     53  
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 = 38, 61, 33, 53)     -1.20  ± 0.46     -0.80  ± 0.38     0.11  ± 0.50     -0.23  ± 0.39  
Week 19 (N = 36, 59, 28, 50)     -1.10  ± 0.47     -0.64  ± 0.38     -0.62  ± 0.52     -1.32  ± 0.39  
Week 32 (N = 32, 51, 26, 41)     -2.11  ± 0.49     -1.45  ± 0.40     -2.18  ± 0.54     -1.93  ± 0.42  
Week 45 (N = 23, 41, 21, 35)     -3.06  ± 0.56     -2.13  ± 0.45     -2.39  ± 0.59     -2.62  ± 0.46  
Week 78 (N = 13, 27, 11, 21)     -5.68  ± 0.71     -3.22  ± 0.54     -4.73  ± 0.77     -2.97  ± 0.56  


Statistical Analysis 1 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.504
Mean Difference (Final Values) [4] 0.40
95% Confidence Interval ( -0.77 to 1.57 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 6.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.592
Mean Difference (Final Values) [4] -0.34
95% Confidence Interval ( -1.58 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.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.441
Mean Difference (Final Values) [4] 0.47
95% Confidence Interval ( -0.72 to 1.65 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 19.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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 4 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.288
Mean Difference (Final Values) [4] -0.69
95% Confidence Interval ( -1.97 to 0.59 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 19.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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[4] 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] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.303
Mean Difference (Final Values) [4] 0.66
95% Confidence Interval ( -0.59 to 1.90 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 32.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 6 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.713
Mean Difference (Final Values) [4] 0.25
95% Confidence Interval ( -1.09 to 1.60 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 32.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 7 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.198
Mean Difference (Final Values) [4] 0.93
95% Confidence Interval ( -0.49 to 2.34 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 45.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 8 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.756
Mean Difference (Final Values) [4] -0.23
95% Confidence Interval ( -1.70 to 1.24 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 45.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 9 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 0.5 mg/kg vs. Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.006
Mean Difference (Final Values) [4] 2.45
95% Confidence Interval ( 0.69 to 4.22 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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Statistical Analysis 10 for Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Groups [1] Placebo/Bapineuzumab 1.0 mg/kg vs. Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Method [2] Mixed Models Analysis
P Value [3] 0.066
Mean Difference (Final Values) [4] 1.75
95% Confidence Interval ( -0.12 to 3.62 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
 

Change from extension study baseline in MMSE score at Week 78.

Results are from a REML based MMRM with change from extension study baseline as the response and the following fixed effect model terms: treatment, visit (scheduled week), treatment-by-visit interaction, baseline value of the response variable, baseline MMSE total score stratum and cholinesterase inhibitor or memantine use stratum.

[2] Other relevant method 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:
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  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
Bapineuzumab program was discontinued prematurely. Efficacy results obtained after Week 78 are not presented due to the very small number of participants after this time point.


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