Trial Outcomes & Findings for A Long-Term Safety And Tolerability Extension Study Of Bapineuzumab In Alzheimer Disease Patients (NCT NCT00998764)

NCT ID: NCT00998764

Last Updated: 2016-01-01

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 494 participants
• Primary outcome timeframe: Up to Week 195
• Results posted on: 2016-01-01

Participant Flow

This study was conducted at 147 centers in 19 countries. The study was terminated early by the sponsor on 06 August 2012. Subjects who had not completed the final follow-up visit prior to 06 August 2012 were asked to complete an early termination visit.

Participant milestones

Measure	Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by intravenous (IV) infusion approximately every 13 weeks up to week 195.	Bapineuzumab/Bapineuzumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Overall Study STARTED	216	276
Overall Study Treated	215	275
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	216	274

Reasons for withdrawal

Measure	Placebo/Bapineuzumab Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by intravenous (IV) infusion approximately every 13 weeks up to week 195.	Bapineuzumab/Bapineuzumab Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Overall Study Lack of Efficacy	3	6
Overall Study Adverse Event	17	12
Overall Study Withdrawal by Subject	19	25
Overall Study Physician Decision	3	3
Overall Study Death	3	1
Overall Study Discontinuation of Study by Sponsor	164	217
Overall Study Protocol Violation	0	1
Overall Study Failed to Return	1	1
Overall Study Lost to Follow-up	1	1
Overall Study Loss of Caregiver	0	3
Overall Study Other	4	4
Overall Study Recurrent Episode of vasogenic edema	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo/Bapineuzumab n=215 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study Bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Bapineuzumab/Bapineuzumab n=275 Participants Participants received Bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Total n=490 Participants Total of all reporting groups
Age, Continuous	71.4 Years STANDARD_DEVIATION 8.14 • n=5 Participants	72.1 Years STANDARD_DEVIATION 7.47 • n=7 Participants	71.8 Years STANDARD_DEVIATION 7.77 • n=5 Participants
Age, Customized < 65 years	44 Participants n=5 Participants	42 Participants n=7 Participants	86 Participants n=5 Participants
Age, Customized >= 65 years	171 Participants n=5 Participants	233 Participants n=7 Participants	404 Participants n=5 Participants
Sex: Female, Male Female	135 Participants n=5 Participants	186 Participants n=7 Participants	321 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	89 Participants n=7 Participants	169 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 195

Population: Safety population

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.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=275 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=215 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Number of Participants Reporting a Serious Adverse Event	33 Number of Participants	35 Number of Participants

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 13, 26, 39, 52 and 78

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

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.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
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= 197, 253)	6.28 Units on a scale Standard Error 0.50	5.53 Units on a scale Standard Error 0.57
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 = 154, 221)	7.70 Units on a scale Standard Error 0.54	7.41 Units on a scale Standard Error 0.63
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 = 121, 184)	8.87 Units on a scale Standard Error 0.61	8.83 Units on a scale Standard Error 0.72
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 = 91, 139)	10.11 Units on a scale Standard Error 0.63	10.12 Units on a scale Standard Error 0.75
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 = 52, 80)	12.70 Units on a scale Standard Error 0.80	13.91 Units on a scale Standard Error 0.96

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 13, 26, 39, 52 and 78

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

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.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. Week 13 (N = 197, 253)	0.73 Units on a scale Standard Error 0.32	0.89 Units on a scale Standard Error 0.36
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. Week 26 (N = 154, 221)	2.19 Units on a scale Standard Error 0.35	2.87 Units on a scale Standard Error 0.42
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. Week 39 (N = 121, 184)	3.35 Units on a scale Standard Error 0.42	4.26 Units on a scale Standard Error 0.50
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. Week 52 (N = 91, 139)	4.51 Units on a scale Standard Error 0.45	5.42 Units on a scale Standard Error 0.55
Change From Extension Study Baseline in ADAS-Cog/11 at Weeks 13, 26, 39, 52 and 78. Week 78 (N = 52, 80)	7.07 Units on a scale Standard Error 0.66	9.21 Units on a scale Standard Error 0.82

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 13, 26, 39, 52 and 78

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

The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 13 (N = 194, 247)	15.32 Units on a scale Standard Error 1.11	-12.33 Units on a scale Standard Error 1.27
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 26 (N = 151, 222)	-18.04 Units on a scale Standard Error 1.11	-15.37 Units on a scale Standard Error 1.29
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 39 (N = 119, 180)	-21.33 Units on a scale Standard Error 1.24	-17.74 Units on a scale Standard Error 1.47
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 52 (N = 89, 137)	-22.72 Units on a scale Standard Error 1.36	-20.96 Units on a scale Standard Error 1.65
Change From Base Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 78 (N = 50, 81)	-29.11 Units on a scale Standard Error 1.75	-26.33 Units on a scale Standard Error 2.18

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 13, 26, 39, 52 and 78

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

The DAD measures instrumental and basic activities of daily living in AD participants. The DAD is administered to the participant's caregiver in the form of an interview. The performance of basic activities of daily living is evaluated in 10 aspects including hygiene, dressing, continence, eating, meal preparation, telephoning, going on an outing, finance and correspondence, medications, leisure, and housework. The caregiver answers 40 questions as yes, no, or not applicable. A one-point score was assigned to each question if the answer is "yes" and a zero score was assigned if the answer is "no". For questions answered as "not applicable", no score will be assigned. The DAD total score was calculated as the total number of questions answered as "yes" divided by the total number of questions answered as "yes" or "no", times 100. The DAD score can range from 0 to 100, with higher scores indicating better function. A positive change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 13 (N = 194, 247)	-3.71 Units on scale Standard Error 0.73	-2.63 Units on scale Standard Error 0.83
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 26 (N = 151, 222)	-6.46 Units on scale Standard Error 0.86	-5.76 Units on scale Standard Error 1.01
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 39 (N = 119, 180)	-9.72 Units on scale Standard Error 1.02	-8.17 Units on scale Standard Error 1.22
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 52 (N = 89, 137)	-11.11 Units on scale Standard Error 1.10	-11.82 Units on scale Standard Error 1.34
Change From Extension Study Baseline in Disability Assessment for Dementia (DAD) Score at Weeks 13, 26, 39, 52 and 78. Week 78 (N = 50, 81)	-17.48 Units on scale Standard Error 1.56	-17.34 Units on scale Standard Error 1.94

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 26, 52 and 78

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

NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. Week 26 (N = 176, 240)	2.95 Units on a scale Standard Error 0.83	2.84 Units on a scale Standard Error 0.97
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. Week 52 (N = 110, 163)	3.52 Units on a scale Standard Error 0.80	4.32 Units on a scale Standard Error 0.96
Change From Base Study Baseline in Neuropsychiatric Inventory (NPI) Score at Weeks 26, 52 and 78. Week 78 (N = 51, 81)	4.93 Units on a scale Standard Error 1.36	6.95 Units on a scale Standard Error 1.70

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 26, 52 and 78

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

NPI:12-domain caregiver assessment of behavioral disturbances occurring in dementia: delusions, hallucinations, agitation/ aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/ indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating, nighttime behavior. Severity(1=Mild to 3=Severe),frequency (1=occasionally to 4=very frequently) scales recorded for each domain; frequency*severity=each domain score(range 0-12). The NPI total score ranges from 0 to 144 with higher NPI scores indicate greater impairment. A negative change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. Week 26 (N = 176, 240)	1.47 Units on a scale Standard Error 0.73	2.17 Units on a scale Standard Error 0.86
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. Week 52 (N = 110, 163)	1.98 Units on a scale Standard Error 0.79	3.82 Units on a scale Standard Error 0.95
Change From Extension Study Baseline in NPI Score at Weeks 26, 52 and 78. Week 78 (N = 51, 81)	3.29 Units on a scale Standard Error 1.35	6.60 Units on a scale Standard Error 1.69

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 6, 19, 32, 45 and 78

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

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. Week 6 (N= 197, 255)	-2.55 Units on a scale Standard Error 0.19	-2.61 Units on a scale Standard Error 0.22
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. Week 19 (N = 184, 241)	-3.01 Units on a scale Standard Error 0.19	-3.13 Units on a scale Standard Error 0.22
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. Week 32 (N = 141, 204)	-3.65 Units on a scale Standard Error 0.20	-3.75 Units on a scale Standard Error 0.24
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. Week 45 (N = 117, 171)	-4.26 Units on a scale Standard Error 0.21	-4.44 Units on a scale Standard Error 0.26
Change From Base Study Baseline in Mini-mental State Examination (MMSE) Score at Weeks 6, 19, 32, 45 and 78. Week 78 (N = 65, 94)	-5.54 Units on a scale Standard Error 0.26	-5.50 Units on a scale Standard Error 0.32

SECONDARY outcome

Timeframe: Base Study Baseline, Weeks 6, 19, 32, 45 and 78

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

MMSE measured general cognitive functioning: orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two intersecting polygons. The MMSE total score can range from 0 to 30, with lower scores indicating a greater degree of impairment. A positive change indicates improvement from baseline.

Outcome measures

Measure	Bapineuzumab/Bapineuzumab n=256 Participants Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Placebo/Bapineuzumab n=199 Participants Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. Week 6 (N = 195, 255)	-0.26 Units on a scale Standard Error 0.16	-0.67 Units on a scale Standard Error 0.19
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. Week 19 (N = 182, 241)	-0.69 Units on a scale Standard Error 0.18	-1.16 Units on a scale Standard Error 0.21
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. Week 32 (N = 140, 204)	-1.40 Units on a scale Standard Error 0.20	-1.85 Units on a scale Standard Error 0.24
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. Week 45 (N = 116, 171)	-2.05 Units on a scale Standard Error 0.24	-2.57 Units on a scale Standard Error 0.28
Change From Extension Study Baseline in MMSE Score at Weeks 6, 19, 32, 45 and 78. Week 78 (N = 64, 94)	-3.42 Units on a scale Standard Error 0.32	-3.69 Units on a scale Standard Error 0.39

Adverse Events

Placebo/Bapineuzumab

Serious events: 35 serious events

Other events: 57 other events

Deaths: 0 deaths

Bapineuzumab/Bapineuzumab

Serious events: 33 serious events

Other events: 45 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo/Bapineuzumab n=215 participants at risk Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Bapineuzumab/Bapineuzumab n=275 participants at risk Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Cardiac disorders Aortic valve stenosis	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial flutter	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrioventricular block	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac failure congestive	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiomyopathy	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Cardiac disorders Mitral valve disease	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.93% 2/215 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haemorrhoids	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Asthenia	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Gait disturbance	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.47% 1/215 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic steatosis	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastritis viral	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Peritonsillar abscess	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.93% 2/215 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Alcohol poisoning	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Forearm fracture	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Subdural haematoma	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Blood creatinine increased	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to peritoneum	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Carotid artery stenosis	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebellar infarction	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemorrhage	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral infarction	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral microhaemorrhage	0.93% 2/215 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 2/275 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Epilepsy	1.4% 3/215 • Number of events 3 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Ischaemic stroke	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lacunar infarction	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lumbar radiculopathy	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Multiple system atrophy	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Partial seizures	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Presyncope	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Subarachnoid haemorrhage	0.93% 2/215 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/275 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Vasogenic cerebral oedema	2.8% 6/215 • Number of events 6 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 2/275 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Aggression	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 2/275 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Agitation	0.47% 1/215 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 2/275 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Confusional state	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.73% 2/275 • Number of events 2 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Delusion	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hallucination	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mental status changes	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mood swings	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Incontinence	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Peripheral artery stenosis	0.00% 0/215 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.36% 1/275 • Number of events 1 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Placebo/Bapineuzumab n=215 participants at risk Participants received placebo in the base study and bapineuzumab in this extension study. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.	Bapineuzumab/Bapineuzumab n=275 participants at risk Participants received bapinezumab in both the base and extension studies. In this extension study bapineuzumab 0.5 mg/kg was administered by IV infusion approximately every 13 weeks up to week 195.
Gastrointestinal disorders Diarrhoea	5.6% 12/215 • Number of events 12 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	3.6% 10/275 • Number of events 13 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral microhaemorrhage	8.4% 18/215 • Number of events 22 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	5.5% 15/275 • Number of events 16 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	7.4% 16/215 • Number of events 29 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 8/275 • Number of events 8 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Vasogenic cerebral oedema	7.9% 17/215 • Number of events 24 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 8/275 • Number of events 8 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	5.1% 11/215 • Number of events 13 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.5% 7/275 • Number of events 7 • 3 years 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 subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Additional Information

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Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER