ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 28 of 31 for:    alzheimer dijon

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00996918
Recruitment Status : Terminated (The study was terminated on August 6, 2012, because 2 large Phase 3 studies showed no clinical benefit. This decision was not based on any new safety concerns.)
First Posted : October 16, 2009
Results First Posted : January 1, 2014
Last Update Posted : January 1, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Alzheimer Disease
Interventions Drug: Bapineuzumab 0.5 mg/kg
Drug: Bapineuzumab 1.0 m/kg
Enrollment 198
Recruitment Details 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 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.
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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. 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.
Period Title: Overall Study
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
Reason Not Completed
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
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 38 62 33 53 4 190
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 38 participants 62 participants 33 participants 53 participants 4 participants 190 participants
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  
Measure Type: Number
Unit of measure:  Number of participants
Number Analyzed 38 participants 62 participants 33 participants 53 participants 4 participants 190 participants
< 65 17 15 12 17 1 62
>= 65 21 47 21 36 3 128
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 38 participants 62 participants 33 participants 53 participants 4 participants 190 participants
Female
13
  34.2%
28
  45.2%
14
  42.4%
19
  35.8%
3
  75.0%
77
  40.5%
Male
25
  65.8%
34
  54.8%
19
  57.6%
34
  64.2%
1
  25.0%
113
  59.5%
1.Primary Outcome
Title Number of Participants Reporting a Serious Adverse Event.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
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.
Overall Number of Participants Analyzed 39 66 37 56 4
Measure Type: Number
Unit of Measure: Number of participants
6 10 1 11 0
2.Secondary Outcome
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.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.390
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-4.29 to 1.68
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.264
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.80
Confidence Interval (2-Sided) 95%
-1.37 to 4.97
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.357
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.51
Confidence Interval (2-Sided) 95%
-4.74 to 1.72
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.981
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-3.50 to 3.42
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.584
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.95
Confidence Interval (2-Sided) 95%
-4.37 to 2.47
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.392
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
-2.05 to 5.20
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.345
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.05
Confidence Interval (2-Sided) 95%
-6.34 to 2.24
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.922
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-4.73 to 4.28
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.384
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.44
Confidence Interval (2-Sided) 95%
-7.97 to 3.10
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.961
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-6.08 to 5.78
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.837
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
-1.91 to 2.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
-0.13 to 4.41
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.990
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-2.32 to 2.35
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.817
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-2.22 to 2.82
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.697
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
-2.04 to 3.05
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.158
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.93
Confidence Interval (2-Sided) 95%
-0.76 to 4.63
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.829
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-4.06 to 3.26
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.950
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-3.69 to 3.93
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.816
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.56
Confidence Interval (2-Sided) 95%
-5.35 to 4.23
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.751
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
-4.32 to 5.96
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-7.22 to 7.53
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.593
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.13
Confidence Interval (2-Sided) 95%
-5.72 to 9.98
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.968
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-7.32 to 7.62
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.473
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.92
Confidence Interval (2-Sided) 95%
-10.92 to 5.08
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.630
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.95
Confidence Interval (2-Sided) 95%
-9.91 to 6.02
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.293
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.53
Confidence Interval (2-Sided) 95%
-13.02 to 3.95
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.733
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.53
Confidence Interval (2-Sided) 95%
-7.28 to 10.33
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.550
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.81
Confidence Interval (2-Sided) 95%
-12.06 to 6.45
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.902
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
-11.04 to 12.50
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.430
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -5.07
Confidence Interval (2-Sided) 95%
-17.75 to 7.61
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-6.01 to 3.95
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.177
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.69
Confidence Interval (2-Sided) 95%
-1.68 to 9.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.734
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.89
Confidence Interval (2-Sided) 95%
-6.03 to 4.25
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.595
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.50
Confidence Interval (2-Sided) 95%
-7.06 to 4.05
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.409
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.35
Confidence Interval (2-Sided) 95%
-7.95 to 3.24
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.368
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.74
Confidence Interval (2-Sided) 95%
-8.73 to 3.24
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.458
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.44
Confidence Interval (2-Sided) 95%
-4.01 to 8.89
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.760
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.04
Confidence Interval (2-Sided) 95%
-7.77 to 5.68
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.597
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
-5.67 to 9.86
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.501
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.87
Confidence Interval (2-Sided) 95%
-11.24 to 5.50
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.183
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.60
Confidence Interval (2-Sided) 95%
-8.91 to 1.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.920
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-5.92 to 5.35
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.133
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -4.99
Confidence Interval (2-Sided) 95%
-11.52 to 1.53
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.505
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.34
Confidence Interval (2-Sided) 95%
-4.55 to 9.22
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -12.86
Confidence Interval (2-Sided) 95%
-21.46 to -4.25
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.760
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.47
Confidence Interval (2-Sided) 95%
-7.95 to 10.88
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.373
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.08
Confidence Interval (2-Sided) 95%
-6.68 to 2.52
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.677
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-5.92 to 3.86
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.280
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.40
Confidence Interval (2-Sided) 95%
-9.61 to 2.80
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.950
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
-6.34 to 6.76
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.06
Confidence Interval (2-Sided) 95%
-23.16 to 3.05
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.732
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
-11.97 to 16.94
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.938
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-1.12 to 1.21
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.753
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-1.43 to 1.04
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.809
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-1.04 to 1.33
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.421
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.52
Confidence Interval (2-Sided) 95%
-1.80 to 0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.535
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
-0.85 to 1.63
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.445
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
-0.82 to 1.86
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.309
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
-0.67 to 2.12
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.872
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-1.34 to 1.57
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.52
Confidence Interval (2-Sided) 95%
0.79 to 4.26
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
0.25 to 3.93
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.
Hide 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 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
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 38 62 33 53
Least Squares Mean (Standard Error)
Unit of Measure: Units on a scale
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)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.504
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
-0.77 to 1.57
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.592
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.34
Confidence Interval (2-Sided) 95%
-1.58 to 0.90
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.441
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
-0.72 to 1.65
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.288
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.69
Confidence Interval (2-Sided) 95%
-1.97 to 0.59
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.303
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
-0.59 to 1.90
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.713
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-1.09 to 1.60
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.198
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
-0.49 to 2.34
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.756
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.23
Confidence Interval (2-Sided) 95%
-1.70 to 1.24
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 0.5 mg/kg, Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.45
Confidence Interval (2-Sided) 95%
0.69 to 4.22
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Bapineuzumab 1.0 mg/kg, Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg
Comments

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.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
-0.12 to 3.62
Estimation Comments [Not Specified]
Time Frame 2.6 years
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title 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
Hide Arm/Group Description 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. 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. 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. 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. 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.
All-Cause Mortality
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
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/39 (15.38%)      10/66 (15.15%)      1/37 (2.70%)      11/56 (19.64%)      0/4 (0.00%)    
Cardiac disorders           
Myocardial infarction * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Gastrointestinal disorders           
Large intestine perforation * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
General disorders           
Chest pain * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  2 0/4 (0.00%)  0
Injury, poisoning and procedural complications           
Chest injury * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Fall * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Femur fracture * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Hip fracture * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Skull fracture * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Subdural haematoma * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 3/56 (5.36%)  3 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Polymyalgia rheumatica * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Rhabdomyolysis * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Basal cell carcinoma * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Bladder cancer * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Metastatic squamous cell carcinoma * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Pancreatic neoplasm * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders           
Cerebellar infarction * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Dementia * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Epilepsy * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Ischaemic stroke * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Loss of consciousness * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Partial seizures with secondary generalisation * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Subarachnoid haemorrhage * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Vasogenic cerebral oedema * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 1/37 (2.70%)  1 0/56 (0.00%)  0 0/4 (0.00%)  0
Psychiatric disorders           
Disorientation * 1  1/39 (2.56%)  1 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Suicidal ideation * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Pulmonary embolism * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders           
Deep vein thrombosis * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Phlebitis * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 0/4 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   18/39 (46.15%)      21/66 (31.82%)      15/37 (40.54%)      15/56 (26.79%)      3/4 (75.00%)    
Blood and lymphatic system disorders           
Anaemia * 1  2/39 (5.13%)  2 1/66 (1.52%)  1 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Eye disorders           
Arteriosclerotic retinopathy * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 1/4 (25.00%)  1
Cataract * 1  0/39 (0.00%)  0 2/66 (3.03%)  3 0/37 (0.00%)  0 0/56 (0.00%)  0 1/4 (25.00%)  1
Gastrointestinal disorders           
Nausea * 1  2/39 (5.13%)  2 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
General disorders           
Gait disturbance * 1  3/39 (7.69%)  3 0/66 (0.00%)  0 1/37 (2.70%)  1 0/56 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations           
Cystitis * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 1/56 (1.79%)  1 1/4 (25.00%)  1
Gastroenteritis * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 3/37 (8.11%)  3 0/56 (0.00%)  0 0/4 (0.00%)  0
Nasopharyngitis * 1  3/39 (7.69%)  3 1/66 (1.52%)  1 1/37 (2.70%)  2 2/56 (3.57%)  2 0/4 (0.00%)  0
Urinary tract infection * 1  2/39 (5.13%)  2 7/66 (10.61%)  7 1/37 (2.70%)  2 0/56 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications           
Fall * 1  0/39 (0.00%)  0 3/66 (4.55%)  6 2/37 (5.41%)  2 3/56 (5.36%)  3 0/4 (0.00%)  0
Metabolism and nutrition disorders           
Folate deficiency * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 1/4 (25.00%)  1
Hypercholesterolaemia * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 1/4 (25.00%)  1
Nervous system disorders           
Cerebral microhaemorrhage * 1  0/39 (0.00%)  0 1/66 (1.52%)  2 0/37 (0.00%)  0 3/56 (5.36%)  3 1/4 (25.00%)  1
Cognitive disorder * 1  1/39 (2.56%)  1 2/66 (3.03%)  3 2/37 (5.41%)  2 3/56 (5.36%)  3 0/4 (0.00%)  0
Dizziness * 1  1/39 (2.56%)  1 4/66 (6.06%)  4 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Headache * 1  1/39 (2.56%)  1 1/66 (1.52%)  1 3/37 (8.11%)  4 2/56 (3.57%)  2 0/4 (0.00%)  0
Presyncope * 1  0/39 (0.00%)  0 1/66 (1.52%)  1 2/37 (5.41%)  2 0/56 (0.00%)  0 0/4 (0.00%)  0
Vasogenic cerebral oedema * 1  2/39 (5.13%)  2 2/66 (3.03%)  2 5/37 (13.51%)  5 3/56 (5.36%)  3 0/4 (0.00%)  0
Psychiatric disorders           
Aggression * 1  2/39 (5.13%)  3 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Delusion * 1  3/39 (7.69%)  3 3/66 (4.55%)  3 0/37 (0.00%)  0 0/56 (0.00%)  0 0/4 (0.00%)  0
Depression * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 2/37 (5.41%)  3 0/56 (0.00%)  0 0/4 (0.00%)  0
Reproductive system and breast disorders           
Benign prostatic hyperplasia * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 1/37 (2.70%)  1 0/56 (0.00%)  0 1/4 (25.00%)  1
Respiratory, thoracic and mediastinal disorders           
Cough * 1  2/39 (5.13%)  3 0/66 (0.00%)  0 0/37 (0.00%)  0 2/56 (3.57%)  2 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders           
Rash erythematous * 1  0/39 (0.00%)  0 0/66 (0.00%)  0 0/37 (0.00%)  0 0/56 (0.00%)  0 1/4 (25.00%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00996918     History of Changes
Other Study ID Numbers: 3133K1-3002
B2521003
First Submitted: October 14, 2009
First Posted: October 16, 2009
Results First Submitted: November 12, 2013
Results First Posted: January 1, 2014
Last Update Posted: January 1, 2014