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

Conditions

Alzheimer Disease

Keywords

antibody

Brief summary

The purpose of this study is to assess the long-term safety and tolerability of bapineuzumab in subjects with Alzheimer Disease who participated in study 3133K1-3000 (NCT00667810). Over 250 sites will participate in over 26 countries. Subjects will receive bapineuzumab. Each subject's participation will last approximately 4 years.

Adrian Ivanoiu, Jérémie Pariente, Kevin Booth, Kasia Lobello, Gérald Luscan et al. (13 authors)

Alzheimer s Research & Therapy2016-06-1638 citations

10.1186/s13195-016-0193-y

Interventions

DRUGBapineuzumab 0.5 mg/kg

Bapineuzumab I.V., 0.5 mg/kg, infusion every 13 weeks for a total of 16 infusions.

DRUGBapineuzumab 1.0 m/kg

I.V., 1.0 mg/kg, infusion every 13 weeks for a total of 16 infusions.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

51 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Subject has completed study 3133K1-3000 and brain magnetic resonance imaging (MRI) scan consistent with the diagnosis of Alzheimer Disease * Mini-Mental Status Examination (MMSE) \>=10 at screening * Caregiver able to attend all clinic visits with subject

Exclusion criteria

* Any medical or psychiatric contraindication or clinically significant abnormality that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study or could preclude the evaluation of the subject's response. * Any significant brain MRI abnormality. * Use of any investigational drugs or devices, other than bapineuzumab within the last 60 days prior to screening

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reporting a Serious Adverse Event.	Up to Week 195	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.

Secondary

Measure	Time frame	Description
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Weeks 13, 26, 39, 52 and 78	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.
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Weeks 13, 26, 39, 52 and 78	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
Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Weeks 13, 26, 39, 52 and 78	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
Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Weeks 13, 26, 39, 52 and 78	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.
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Weeks 26, 52 and 78	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.
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Weeks 6, 19, 32, 45 and 78	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.
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Weeks 6, 19, 32, 45 and 78	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
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Weeks 26, 52 and 78	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.

Countries

Australia, Belgium, Chile, Finland, France, Italy, Japan, Netherlands, New Zealand, Poland, Portugal, Slovakia, South Africa, Spain, Sweden, Switzerland, United Kingdom

Participant flow

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.

Participants by arm

Arm	Count
Placebo/Bapineuzumab 0.5 mg/kg Participants received placebo in the base study and 0.5 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.	38
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg Participants received 0.5 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.	62
Placebo/Bapineuzumab 1.0 mg/kg Participants received placebo in the base study and 1.0 mg/kg bapineuzumab in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.	33
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants received 1.0 mg/kg bapineuzumab in both the base and extension studies. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.	53
Bapineuzumab 2.0 mg/kg/Bapineuzumab 1.0 mg/kg Participants originally randomized to 2.0 mg/kg bapineuzumab were reassigned to the 1.0 mg/kg dose level after discontinuation of 2.0 mg/kg dose level in the base study and continued the 1.0 mg/kg dose in this extension study. In this extension study bapineuzumab was administered by IV infusion approximately every 13 weeks up to Week 195.	4
Total	190

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	2	5	2	6	0
Overall Study	Discontinuation of Study by Sponsor	31	54	30	45	2
Overall Study	Lack of Efficacy	1	1	2	2	0
Overall Study	Loss of Caregiver	0	1	0	0	0
Overall Study	Other	3	1	0	0	0
Overall Study	Physician Decision	1	0	0	0	0
Overall Study	Withdrawal by Subject	1	4	3	3	2

Baseline characteristics

Characteristic	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
Age Continuous	68.9 Years STANDARD_DEVIATION 9.7	71.9 Years STANDARD_DEVIATION 8.83	68.8 Years STANDARD_DEVIATION 8.59	70.6 Years STANDARD_DEVIATION 9.13	71.3 Years STANDARD_DEVIATION 10.63	70.4 Years STANDARD_DEVIATION 9.08
Age, Customized < 65	17 Number of participants	15 Number of participants	12 Number of participants	17 Number of participants	1 Number of participants	62 Number of participants
Age, Customized >= 65	21 Number of participants	47 Number of participants	21 Number of participants	36 Number of participants	3 Number of participants	128 Number of participants
Sex: Female, Male Female	13 Participants	28 Participants	14 Participants	19 Participants	3 Participants	77 Participants
Sex: Female, Male Male	25 Participants	34 Participants	19 Participants	34 Participants	1 Participants	113 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	18 / 39	21 / 66	15 / 37	15 / 56	3 / 4
serious Total, serious adverse events	6 / 39	10 / 66	1 / 37	11 / 56	0 / 4

Outcome results

Primary

Number of Participants Reporting a Serious Adverse Event.

Safety was measured according to standard adverse event collection as described in the Adverse Event Section of the Results. Complete tables of events are provided there.

Time frame: Up to Week 195

Population: 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	Measure	Value (NUMBER)
Placebo/Bapineuzumab 0.5 mg/kg	Number of Participants Reporting a Serious Adverse Event.	6 Number of participants
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Number of Participants Reporting a Serious Adverse Event.	10 Number of participants
Placebo/Bapineuzumab 1.0 mg/kg	Number of Participants Reporting a Serious Adverse Event.	1 Number of participants
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Number of Participants Reporting a Serious Adverse Event.	11 Number of participants
Bapineuzumab 2.0 mg/kg/ Bapineuzumab 1.0 mg/kg	Number of Participants Reporting a Serious Adverse Event.	0 Number of participants

Secondary

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

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	12.44 Units on a scale	Standard Error 1.7
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	9.00 Units on a scale	Standard Error 1.27
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	7.47 Units on a scale	Standard Error 1.17
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	14.71 Units on a scale	Standard Error 2.12
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	9.74 Units on a scale	Standard Error 1.35
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	10.38 Units on a scale	Standard Error 1.35
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	7.49 Units on a scale	Standard Error 1.03
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	12.27 Units on a scale	Standard Error 1.81
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	8.79 Units on a scale	Standard Error 1.08
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	6.17 Units on a scale	Standard Error 0.95
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	15.46 Units on a scale	Standard Error 2.46
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	4.66 Units on a scale	Standard Error 1.26
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	7.34 Units on a scale	Standard Error 1.38
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	7.92 Units on a scale	Standard Error 1.45
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	10.54 Units on a scale	Standard Error 1.82
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	15.31 Units on a scale	Standard Error 1.68
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	7.30 Units on a scale	Standard Error 1.07
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	9.50 Units on a scale	Standard Error 1.12
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	10.31 Units on a scale	Standard Error 1.36
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Alzheimer's Disease Assesment Scale-Cognitive Subscale (ADAS-Cog/11) at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	6.45 Units on a scale	Standard Error 0.98

Comparison: 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.p-value: 0.3995% CI: [-4.29, 1.68]Mixed Models Analysis

Comparison: 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.p-value: 0.26495% CI: [-1.37, 4.97]Mixed Models Analysis

Comparison: 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.p-value: 0.35795% CI: [-4.74, 1.72]Mixed Models Analysis

Comparison: 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.p-value: 0.98195% CI: [-3.5, 3.42]Mixed Models Analysis

Comparison: 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.p-value: 0.58495% CI: [-4.37, 2.47]Mixed Models Analysis

Comparison: 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.p-value: 0.39295% CI: [-2.05, 5.2]Mixed Models Analysis

Comparison: 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.p-value: 0.34595% CI: [-6.34, 2.24]Mixed Models Analysis

Comparison: 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.p-value: 0.92295% CI: [-4.73, 4.28]Mixed Models Analysis

Comparison: 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.p-value: 0.38495% CI: [-7.97, 3.1]Mixed Models Analysis

Comparison: 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.p-value: 0.96195% CI: [-6.08, 5.78]Mixed Models Analysis

Secondary

Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 56, 26, 44)	-21.19 Units on a scale	Standard Error 2.93
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 30)	-29.52 Units on a scale	Standard Error 3.48
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 21, 37)	-25.42 Units on a scale	Standard Error 3.14
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 20, 8, 20)	-36.48 Units on a scale	Standard Error 4.56
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 31, 52)	-18.75 Units on a scale	Standard Error 2.88
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 20, 8, 20)	-35.75 Units on a scale	Standard Error 3.79
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 21, 37)	-27.36 Units on a scale	Standard Error 2.51
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 31, 52)	-18.60 Units on a scale	Standard Error 2.36
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 56, 26, 44)	-21.04 Units on a scale	Standard Error 2.38
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 30)	-28.00 Units on a scale	Standard Error 2.77
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 20, 8, 20)	-25.21 Units on a scale	Standard Error 5.24
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 31, 52)	-15.50 Units on a scale	Standard Error 3.13
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 56, 26, 44)	-16.26 Units on a scale	Standard Error 3.19
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 21, 37)	-14.57 Units on a scale	Standard Error 3.39
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 30)	-20.41 Units on a scale	Standard Error 3.74
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 21, 37)	-19.10 Units on a scale	Standard Error 2.62
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 56, 26, 44)	-19.18 Units on a scale	Standard Error 2.48
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 31, 52)	-13.36 Units on a scale	Standard Error 2.43
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 20, 8, 20)	-30.28 Units on a scale	Standard Error 3.65
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 30)	-23.21 Units on a scale	Standard Error 2.8

Comparison: 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.p-value: 0.96795% CI: [-7.22, 7.53]Mixed Models Analysis

Comparison: 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.p-value: 0.59395% CI: [-5.72, 9.98]Mixed Models Analysis

Comparison: 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.p-value: 0.96895% CI: [-7.32, 7.62]Mixed Models Analysis

Comparison: 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.p-value: 0.47395% CI: [-10.92, 5.08]Mixed Models Analysis

Comparison: 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.p-value: 0.6395% CI: [-9.91, 6.02]Mixed Models Analysis

Comparison: 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.p-value: 0.29395% CI: [-13.02, 3.95]Mixed Models Analysis

Comparison: 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.p-value: 0.73395% CI: [-7.28, 10.33]Mixed Models Analysis

Comparison: 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.p-value: 0.5595% CI: [-12.06, 6.45]Mixed Models Analysis

Comparison: 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.p-value: 0.90295% CI: [-11.04, 12.5]Mixed Models Analysis

Comparison: 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.p-value: 0.4395% CI: [-17.75, 7.61]Mixed Models Analysis

Secondary

Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-2.80 Units on a scale	Standard Error 0.47
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-2.89 Units on a scale	Standard Error 0.46
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-7.62 Units on a scale	Standard Error 0.7
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-4.86 Units on a scale	Standard Error 0.56
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-3.82 Units on a scale	Standard Error 0.49
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-2.85 Units on a scale	Standard Error 0.37
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-5.10 Units on a scale	Standard Error 0.54
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-4.13 Units on a scale	Standard Error 0.44
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-2.66 Units on a scale	Standard Error 0.38
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-3.43 Units on a scale	Standard Error 0.4
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-2.76 Units on a scale	Standard Error 0.51
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-4.63 Units on a scale	Standard Error 0.58
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-4.40 Units on a scale	Standard Error 0.53
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-2.02 Units on a scale	Standard Error 0.49
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-6.97 Units on a scale	Standard Error 0.75
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-4.89 Units on a scale	Standard Error 0.56
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-3.29 Units on a scale	Standard Error 0.39
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-4.51 Units on a scale	Standard Error 0.46
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-3.88 Units on a scale	Standard Error 0.42
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-2.22 Units on a scale	Standard Error 0.39

Comparison: 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.p-value: 0.93895% CI: [-1.12, 1.21]Mixed Models Analysis

Comparison: 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.p-value: 0.75395% CI: [-1.43, 1.04]Mixed Models Analysis

Comparison: 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.p-value: 0.80995% CI: [-1.04, 1.33]Mixed Models Analysis

Comparison: 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.p-value: 0.42195% CI: [-1.8, 0.75]Mixed Models Analysis

Comparison: 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.p-value: 0.53595% CI: [-0.85, 1.63]Mixed Models Analysis

Comparison: 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.p-value: 0.44595% CI: [-0.82, 1.86]Mixed Models Analysis

Comparison: 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.p-value: 0.30995% CI: [-0.67, 2.12]Mixed Models Analysis

Comparison: 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.p-value: 0.87295% CI: [-1.34, 1.57]Mixed Models Analysis

Comparison: 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.p-value: 0.00495% CI: [0.79, 4.26]Mixed Models Analysis

Comparison: 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.p-value: 0.02695% CI: [0.25, 3.93]Mixed Models Analysis

Secondary

Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 59, 30, 51)	4.57 Units on a scale	Standard Error 2.08
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	16.17 Units on a scale	Standard Error 3.23
Placebo/Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	4.99 Units on a scale	Standard Error 2.6
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 59, 30, 51)	0.97 Units on a scale	Standard Error 1.7
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	3.31 Units on a scale	Standard Error 2.94
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	-0.01 Units on a scale	Standard Error 2.05
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	4.23 Units on a scale	Standard Error 2.8
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 59, 30, 51)	4.71 Units on a scale	Standard Error 2.26
Placebo/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	5.24 Units on a scale	Standard Error 4.02
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 59, 30, 51)	4.43 Units on a scale	Standard Error 1.75
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	6.70 Units on a scale	Standard Error 2.61
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	6.57 Units on a scale	Standard Error 2.08

Comparison: 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.p-value: 0.18395% CI: [-8.91, 1.71]Mixed Models Analysis

Comparison: 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.p-value: 0.9295% CI: [-5.92, 5.35]Mixed Models Analysis

Comparison: 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.p-value: 0.13395% CI: [-11.52, 1.53]Mixed Models Analysis

Comparison: 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.p-value: 0.50595% CI: [-4.55, 9.22]Mixed Models Analysis

Comparison: 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.p-value: 0.00395% CI: [-21.46, -4.25]Mixed Models Analysis

Comparison: 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.p-value: 0.7695% CI: [-7.95, 10.88]Mixed Models Analysis

Secondary

Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	0.10 Units on a scale	Standard Error 0.84
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	1.61 Units on a scale	Standard Error 0.92
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	2.35 Units on a scale	Standard Error 1.01
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	4.85 Units on a scale	Standard Error 1.45
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	7.29 Units on a scale	Standard Error 1.81
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	4.45 Units on a scale	Standard Error 1.14
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	6.73 Units on a scale	Standard Error 1.57
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	2.86 Units on a scale	Standard Error 0.79
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	1.63 Units on a scale	Standard Error 0.75
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	0.32 Units on a scale	Standard Error 0.68
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	4.30 Units on a scale	Standard Error 1.55
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	1.68 Units on a scale	Standard Error 1.07
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	1.08 Units on a scale	Standard Error 1.01
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	8.86 Units on a scale	Standard Error 2.15
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	-1.68 Units on a scale	Standard Error 0.9
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 78 (N = 12, 19, 8, 20)	9.68 Units on a scale	Standard Error 1.42
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 39 (N = 25, 46, 22, 37)	3.62 Units on a scale	Standard Error 0.83
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 26 (N = 33, 54, 26, 45)	1.37 Units on a scale	Standard Error 0.78
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 52 (N = 18, 32, 15, 29)	4.43 Units on a scale	Standard Error 1.14
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.	Week 13 (N = 38, 62, 33, 53)	0.46 Units on a scale	Standard Error 0.7

Comparison: 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.p-value: 0.83795% CI: [-1.91, 2.35]Mixed Models Analysis

Comparison: 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.p-value: 0.06495% CI: [-0.13, 4.41]Mixed Models Analysis

Comparison: 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.p-value: 0.9995% CI: [-2.32, 2.35]Mixed Models Analysis

Comparison: 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.p-value: 0.81795% CI: [-2.22, 2.82]Mixed Models Analysis

Comparison: 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.p-value: 0.69795% CI: [-2.04, 3.05]Mixed Models Analysis

Comparison: 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.p-value: 0.15895% CI: [-0.76, 4.63]Mixed Models Analysis

Comparison: 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.p-value: 0.82995% CI: [-4.06, 3.26]Mixed Models Analysis

Comparison: 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.p-value: 0.9595% CI: [-3.69, 3.93]Mixed Models Analysis

Comparison: 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.p-value: 0.81695% CI: [-5.35, 4.23]Mixed Models Analysis

Comparison: 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.p-value: 0.75195% CI: [-4.32, 5.96]Mixed Models Analysis

Secondary

Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 13 (N = 38, 62, 31, 52)	-3.80 Units on a scale	Standard Error 1.96
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 26 (N = 33, 56, 26, 44)	-6.33 Units on a scale	Standard Error 2.02
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 39 (N = 25, 46, 21, 37)	-11.14 Units on a scale	Standard Error 2.23
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 52 (N = 18, 32, 15, 30)	-16.21 Units on a scale	Standard Error 2.57
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 78 (N = 12, 20, 8, 20)	-23.40 Units on a scale	Standard Error 3.01
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 13 (N = 38, 62, 31, 52)	-4.83 Units on a scale	Standard Error 1.6
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 39 (N = 25, 46, 21, 37)	-13.49 Units on a scale	Standard Error 1.76
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 78 (N = 12, 20, 8, 20)	-21.30 Units on a scale	Standard Error 2.54
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 52 (N = 18, 32, 15, 30)	-13.77 Units on a scale	Standard Error 2.02
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 26 (N = 33, 56, 26, 44)	-7.22 Units on a scale	Standard Error 1.64
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 13 (N = 38, 62, 31, 52)	-5.17 Units on a scale	Standard Error 2.16
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 52 (N = 18, 32, 15, 30)	-10.02 Units on a scale	Standard Error 2.75
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 26 (N = 33, 56, 26, 44)	-5.75 Units on a scale	Standard Error 2.23
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 39 (N = 25, 46, 21, 37)	-4.34 Units on a scale	Standard Error 2.41
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 78 (N = 12, 20, 8, 20)	-14.54 Units on a scale	Standard Error 3.54
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 39 (N = 25, 46, 21, 37)	-7.08 Units on a scale	Standard Error 1.85
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 52 (N = 18, 32, 15, 30)	-11.06 Units on a scale	Standard Error 2.02
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 26 (N = 33, 56, 26, 44)	-7.25 Units on a scale	Standard Error 1.73
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 13 (N = 38, 62, 31, 52)	-1.48 Units on a scale	Standard Error 1.65
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78	Week 78 (N = 12, 20, 8, 20)	-17.41 Units on a scale	Standard Error 2.37

Comparison: 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.p-value: 0.68395% CI: [-6.01, 3.95]Mixed Models Analysis

Comparison: 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.p-value: 0.17795% CI: [-1.68, 9.06]Mixed Models Analysis

Comparison: 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.p-value: 0.73495% CI: [-6.03, 4.25]Mixed Models Analysis

Comparison: 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.p-value: 0.59595% CI: [-7.06, 4.05]Mixed Models Analysis

Comparison: 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.p-value: 0.40995% CI: [-7.95, 3.24]Mixed Models Analysis

Comparison: 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.p-value: 0.36895% CI: [-8.73, 3.24]Mixed Models Analysis

Comparison: 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.p-value: 0.45895% CI: [-4.01, 8.89]Mixed Models Analysis

Comparison: 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.p-value: 0.7695% CI: [-7.77, 5.68]Mixed Models Analysis

Comparison: 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.p-value: 0.59795% CI: [-5.67, 9.86]Mixed Models Analysis

Comparison: 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.p-value: 0.50195% CI: [-11.24, 5.5]Mixed Models Analysis

Secondary

Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-3.06 Units on a scale	Standard Error 0.56
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-5.68 Units on a scale	Standard Error 0.71
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-1.20 Units on a scale	Standard Error 0.46
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-1.10 Units on a scale	Standard Error 0.47
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-2.11 Units on a scale	Standard Error 0.49
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-0.80 Units on a scale	Standard Error 0.38
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-2.13 Units on a scale	Standard Error 0.45
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-3.22 Units on a scale	Standard Error 0.54
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-0.64 Units on a scale	Standard Error 0.38
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-1.45 Units on a scale	Standard Error 0.4
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-2.18 Units on a scale	Standard Error 0.54
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-0.62 Units on a scale	Standard Error 0.52
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-2.39 Units on a scale	Standard Error 0.59
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-4.73 Units on a scale	Standard Error 0.77
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	0.11 Units on a scale	Standard Error 0.5
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 78 (N = 13, 27, 11, 21)	-2.97 Units on a scale	Standard Error 0.56
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 45 (N = 23, 41, 21, 35)	-2.62 Units on a scale	Standard Error 0.46
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 6 (N = 38, 61, 33, 53)	-0.23 Units on a scale	Standard Error 0.39
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 19 (N = 36, 59, 28, 50)	-1.32 Units on a scale	Standard Error 0.39
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.	Week 32 (N = 32, 51, 26, 41)	-1.93 Units on a scale	Standard Error 0.42

Comparison: 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.p-value: 0.50495% CI: [-0.77, 1.57]Mixed Models Analysis

Comparison: 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.p-value: 0.59295% CI: [-1.58, 0.9]Mixed Models Analysis

Comparison: 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.p-value: 0.44195% CI: [-0.72, 1.65]Mixed Models Analysis

Comparison: 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.p-value: 0.28895% CI: [-1.97, 0.59]Mixed Models Analysis

Comparison: 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.p-value: 0.30395% CI: [-0.59, 1.9]Mixed Models Analysis

Comparison: 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.p-value: 0.71395% CI: [-1.09, 1.6]Mixed Models Analysis

Comparison: 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.p-value: 0.19895% CI: [-0.49, 2.34]Mixed Models Analysis

Comparison: 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.p-value: 0.75695% CI: [-1.7, 1.24]Mixed Models Analysis

Comparison: 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.p-value: 0.00695% CI: [0.69, 4.22]Mixed Models Analysis

Comparison: 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.p-value: 0.06695% CI: [-0.12, 3.62]Mixed Models Analysis

Secondary

Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.

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

Population: 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	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	2.34 Units on a scale	Standard Error 2.45
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 60, 30, 51)	2.29 Units on a scale	Standard Error 1.79
Placebo/Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	11.76 Units on a scale	Standard Error 4.86
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	1.70 Units on a scale	Standard Error 4.4
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	-1.06 Units on a scale	Standard Error 1.94
Bapineuzumab 0.5 mg/kg/ Bapineuzumab 0.5 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 60, 30, 51)	0.21 Units on a scale	Standard Error 1.48
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	2.28 Units on a scale	Standard Error 6.07
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 60, 30, 51)	2.77 Units on a scale	Standard Error 1.96
Placebo/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	3.78 Units on a scale	Standard Error 2.65
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 52 (N = 21, 37, 17, 32)	3.99 Units on a scale	Standard Error 1.97
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 78 (N = 13, 18, 8, 20)	4.76 Units on a scale	Standard Error 3.93
Bapineuzumab 1.0 mg/kg/Bapineuzumab 1.0 mg/kg	Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.	Week 26 (N = 36, 60, 30, 51)	1.73 Units on a scale	Standard Error 1.51

Comparison: 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.p-value: 0.37395% CI: [-6.68, 2.52]Mixed Models Analysis

Comparison: 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.p-value: 0.67795% CI: [-5.92, 3.86]Mixed Models Analysis

Comparison: 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.p-value: 0.2895% CI: [-9.61, 2.8]Mixed Models Analysis

Comparison: 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.p-value: 0.9595% CI: [-6.34, 6.76]Mixed Models Analysis

Comparison: 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.p-value: 0.1395% CI: [-23.16, 3.05]Mixed Models Analysis

Comparison: 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.p-value: 0.73295% CI: [-11.97, 16.94]Mixed Models Analysis

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

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

Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78.

Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78.

Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78.

Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78.

Change From Extension Study Baseline in DAD Score at Weeks 13, 26, 39, 52 and 78

Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78.

Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78.