Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of Bapineuzumab in Alzheimer Disease Patients (NCT NCT00676143)

NCT ID: NCT00676143

Last Updated: 2016-06-10

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 1100 participants
• Primary outcome timeframe: Baseline and 78 weeks
• Results posted on: 2016-06-10

Participant Flow

The study was conducted at 218 centers across the world. The study was terminated early by the sponsor on 06 August 2012. Enrollment had already been completed at the time of this decision. Participants who were still participating at that time were asked to complete an early withdrawal visit.

Participant milestones

Measure	Placebo Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Bapineuzumab Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Overall Study STARTED	441	658
Overall Study Treated	439	654
Overall Study COMPLETED	285	398
Overall Study NOT COMPLETED	156	260

Reasons for withdrawal

Measure	Placebo Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Bapineuzumab Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Overall Study Adverse Event	34	60
Overall Study Death	4	4
Overall Study Lack of Efficacy	0	6
Overall Study Lost to Follow-up	0	13
Overall Study Physician Decision	5	8
Overall Study Protocol Violation	4	8
Overall Study Withdrawal by Subject	24	42
Overall Study Discontinuation of study by sponsor	65	88
Overall Study Failed to return	2	1
Overall Study Loss of caregiver	5	3
Overall Study Other	11	20
Overall Study Participant participation unknown	1	4
Overall Study Vasogenic edema recurrence	1	3

Baseline Characteristics

Study Evaluating the Safety and Efficacy of Bapineuzumab in Alzheimer Disease Patients

Baseline characteristics by cohort

Measure	Placebo n=439 Participants Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Bapineuzumab n=654 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Total n=1093 Participants Total of all reporting groups
Age, Continuous	70.3 Years STANDARD_DEVIATION 7.75 • n=5 Participants	71.0 Years STANDARD_DEVIATION 7.67 • n=7 Participants	70.7 Years STANDARD_DEVIATION 7.71 • n=5 Participants
Age, Customized <65 years	97 Number of participants n=5 Participants	132 Number of participants n=7 Participants	229 Number of participants n=5 Participants
Age, Customized >=65 years	342 Number of participants n=5 Participants	522 Number of participants n=7 Participants	864 Number of participants n=5 Participants
Sex: Female, Male Female	262 Participants n=5 Participants	421 Participants n=7 Participants	683 Participants n=5 Participants
Sex: Female, Male Male	177 Participants n=5 Participants	233 Participants n=7 Participants	410 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 78 weeks

Population: The modified intent-to-treat (mITT) included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and Disability Assessment for Dementia (DAD) total score.

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	Placebo n=300 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=414 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog)/11 Subscale Total Score at Week 78	7.31 Unit on a scale Standard Error 0.47	7.32 Unit on a scale Standard Error 0.39

PRIMARY outcome

Timeframe: Baseline and 78 weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

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.

Outcome measures

Measure	Placebo n=301 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=411 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 78	-14.94 Unit on a scale Standard Deviation 1.00	-14.89 Unit on a scale Standard Deviation 0.84

SECONDARY outcome

Timeframe: Baseline and 71 weeks

Population: PIB PET population included all randomized participants who enrolled in the PET substudies and who met the following criteria: a) received at least one infusion or portion of an infusion of study drug, b) had a baseline and at least one postbaseline PIB PET assessment, and c) had an SUVr for the global cortical average (GCA) ROI ≥1.35 at baseline.

Brain amyloid burden as imaged by 11C-Pittsburgh compound B (PIB) positron emission tomography (PET). The latter is a semi-quantitative measure of the extent of fibrillar amyloid in the brain. PIB PET measurements were made in cortical regions found to have the highest burden of fibrillar amyloid at autopsy in participants diagnosed as having Alzheimer's pathology, and also regions reported to have the highest average retention of PIB signal in previous PET studies enrolling participants with probable AD. This parameter reflects overall brain amyloid deposition as indexed by imaging. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by PIB PET imaging in a subset of participants.

Outcome measures

Measure	Placebo n=12 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=15 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Brain Amyloid Burden at Week 71	0.03 standard uptake value ratio Standard Error 0.04	-0.04 standard uptake value ratio Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline and 71 Weeks

Population: CSF population included all randomized participants who enrolled in the CSF substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline CSF measurement (CSF phospho-tau).

Biomarkers CSF phospho-tau is an indicator of neuronal injury and neurodegeneration. An elevation in levels of tau, as well as specific p-tau species, is thought to be a marker for progressive cellular degeneration in AD. Accordingly, a reduction from baseline in levels of CSF tau in participants who received bapineuzumab compared with participants who received placebo may be indicative of a reduction in neuronal loss in participants treated with bapineuzumab.

Outcome measures

Measure	Placebo n=62 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=76 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Cerebrospinal Fluid (CSF) Phospho-tau Levels at Week 71	0.83 pg/mL Standard Error 2.04	-0.55 pg/mL Standard Error 1.84

SECONDARY outcome

Timeframe: Baseline and 71 Weeks

Population: vMRI population included all randomized participants who enrolled in the vMRI substudies, received at least one infusion or portion of an infusion of study drug, and had a baseline and at least one postbaseline vMRI that passed quality control and was satisfactory for volumetric analysis.

Cerebral atrophy correlates closely with the gradual cognitive decline in AD and can be visualized by MRI. The BBSI technique involves positional matching of serial 3-dimensional MRI brain images, such that brain MRI-image volumes were first registered and then subtracted from each other. Atrophy rates would generally be expected to be lower if the underlying disease was attenuated by effective treatment.

Outcome measures

Measure	Placebo n=131 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=197 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Brain Volume, as Assessed by Magnetic Resonance Imaging Brain Boundary Shift Integral (MRI BBSI), at Week 71	17.64 Milliliter (mL)/year Standard Error 0.69	17.51 Milliliter (mL)/year Standard Error 0.56

SECONDARY outcome

Timeframe: Week 39 to Week 78

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. ADAS-Cog/11 total score range is 0 (least impairment) to 70 (most impairment); a negative treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 Week 39	2.95 Units/Year Standard Error 0.30	2.68 Units/Year Standard Error 0.25
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 Week 52	4.40 Units/Year Standard Error 0.34	4.08 Units/Year Standard Error 0.29
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 Week 65	5.76 Units/Year Standard Error 0.39	5.16 Units/Year Standard Error 0.32
Divergence of Effect on the ADAS-Cog/11 Total Scores From Week 39 to Week 78 Week 78	7.31 Units/Year Standard Error 0.47	7.32 Units/Year Standard Error 0.39

SECONDARY outcome

Timeframe: Week 39 to Week 78

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Treatment differences are estimated using least-squares (LS) means with factor levels weighted according to overall analysis population proportions. DAD total score range is 0 to 100; a positive treatment difference (bapineuzumab minus placebo) favors bapineuzumab. Within the MMRMs for ADAS-Cog/11 described for the primary analyses, linear contrasts were formed to test increasing trend of the differences between bapineuzumab and placebo from Week 39 (the 9-month visit) through Week 78 (the 18 -month visit) for each variable, which is equivalent to testing a positive slope of the differences between each bapineuzumab dose group and placebo from Week 39 through Week 78. Results are from a restricted maximum likelihood (REML)-based mixed model for MMRM.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 Week 39	-6.60 Units/Year Standard Error 0.65	-6.93 Units/Year Standard Error 0.54
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 Week 52	-9.34 Units/Year Standard Error 0.73	-9.34 Units/Year Standard Error 0.61
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 Week 65	-12.14 Units/Year Standard Error 0.91	-13.04 Units/Year Standard Error 0.76
Divergence of Effect on the DAD Total Scores From Week 39 to Week 78 Week 78	-14.94 Units/Year Standard Error 1.00	-14.89 Units/Year Standard Error 0.84

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

The time to first median placebo deterioration, defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score greater than or equal to the median worsening observed at Week 78 in the placebo group. The Kaplan Meier estimate of median time to first median placebo deterioration was presented.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Time to First Median Placebo Deterioration on ADAS-Cog/11 Total Score (European Union [EU] Analysis Plan)	463.0 Days Interval 455.0 to 546.0	457.0 Days Interval 455.0 to 541.0

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

The time to first clinically meaningful deterioration was defined as the first time a participant experienced an increase (worsening) from baseline in ADAS-Cog/11 total score of >=7.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Time to First Clinically Meaningful Deterioration on ADAS-Cog/11 Total Score (United States [US] Analysis Plan)	NA Days Interval 546.0 to Values were not calculable due to the large number of censored event times	546.0 Days Interval 546.0 to Values were not calculable due to the large number of censored event times

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

The time to first median placebo deterioration was defined as the first time a participant experienced a decrease (worsening) in DAD total score greater than or equal to the median worsening at Week 78 in the placebo group.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Time to First Median Placebo Deterioration on DAD Total Score (EU Analysis Plan)	464.0 Days Interval 455.0 to 546.0	456.0 Days Interval 449.0 to 539.0

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

The time to first clinically meaningful deterioration was defined as the first time a participant experienced a decrease (worsening) from baseline in DAD total score of >=12.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Time to First Clinically Meaningful Deterioration on DAD Total Score (US Analysis)	546.0 Days Interval 542.0 to 546.0	546.0 Days Interval 540.0 to 546.0

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

The Dependence Scale (DS) is a 13-item, caregiver-rated instrument for determining the amount of support required by a participant with AD. The DS total score ranges from 0 to 15, with higher scores indicating more need for assistance. The DS was administered as an interview to the caregiver at scheduled study visits.

Outcome measures

Measure	Placebo n=316 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=437 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Dependence Scale Total Score at Week 78	1.33 Unit on a scale Standard Error 0.12	1.22 Unit on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Percentage of participants with worsening from baseline to Week 78 in ADAS-Cog/11 total score of ≤0, ≤3, and ≤7 points were reported. In order to calculate time to first median placebo deterioration in ADAS-Cog/11, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the ADAS-Cog/11 total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the ADAS-Cog/11 total score of 7 points or more and the worsening is confirmed by the ADAS-Cog/11 assessment at the next non-missing visit.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (EU Analysis Plan) Worsening of 0 points	18.3 Percentage of participants Interval 14.8 to 22.3	15.5 Percentage of participants Interval 12.8 to 18.6
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (EU Analysis Plan) Worsening of 3 points	30.4 Percentage of participants Interval 26.1 to 35.0	25.5 Percentage of participants Interval 22.2 to 29.1
Percentage of Participants With Worsening From Baseline in ADAS-Cog/11 Total Score at Week 78 (EU Analysis Plan) Worsening of 7 points	42.5 Percentage of participants Interval 37.7 to 47.3	38.0 Percentage of participants Interval 34.3 to 41.9

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Percentage of participants whose increase (worsening) from baseline to Week 78 in ADAS-Cog/11 total score was <7.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Percentage of Responders for ADAS-Cog/11 Total Score at Week 78 (US Analysis Plan)	42.2 Percentage of participant	37.1 Percentage of participant

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score of ≤ 0, ≤ 6, and ≤ 12 points. In order to calculate time to first median placebo deterioration in DAD, the median change from baseline to Week 78 among the placebo participants of the mITT analysis population were determined. The median changes were used as the cutpoints for determining "deterioration" for Alzheimer's disease participants in the study. If the median change from baseline to Week 78 in the DAD total score among the placebo participants of the mITT Analysis Population is 7 points, then the first median placebo deterioration is the first time where there is a worsening on the DAD total score of 7 points or more and the worsening is confirmed by the DAD assessment at the next non-missing visit.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (EU Analysis Plan) Worsening of 0 points	17.2 Percentage of participants Interval 13.7 to 21.1	18.6 Percentage of participants Interval 15.7 to 21.8
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (EU Analysis Plan) Worsening of 6 points	29.9 Percentage of participants Interval 25.6 to 34.5	27.4 Percentage of participants Interval 24.0 to 31.0
Percentage of Participants With Worsening From Baseline in DAD Total Score at Week 78 (EU Analysis Plan) Worsening of 12 points	39.7 Percentage of participants Interval 35.0 to 44.5	34.9 Percentage of participants Interval 31.3 to 38.7

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

Percentage of participants whose decrease (worsening) from baseline to Week 78 in DAD total score was <12.

Outcome measures

Measure	Placebo n=431 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=650 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Percentage of Responders for DAD Total Score at Week 78 (US Analysis Plan)	39.7 Percentage of participant	34.9 Percentage of participant

SECONDARY outcome

Timeframe: Baseline and 78 Weeks

Population: The mITT included all randomized participants who received at least one infusion or portion of an infusion of study drug and who had a baseline and at least one post-baseline assessment of the ADAS-Cog/11 total score and DAD total score.

The CDR-SOB is a global clinical staging instrument that sums 6 clinical ratings: 1) memory, 2) orientation, 3) judgment and problem solving, 4) involvement in community affairs, 5) home and hobbies, and 6) personal care based on the Clinical Dementia Rating Scale (CDR) interview. The CDR includes discussions with the participant and caregiver using a structured format. This scale had to be administered by a trained and certified global rater who did not have access to any information regarding adverse events experienced by the participant. CDR-SOB total score range is 0 (least impairment) to 18 (most impairment); a negative change from baseline indicates an improvement.

Outcome measures

Measure	Placebo n=310 Participants Participants received placebo by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks	Bapineuzumab n=427 Participants Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SOB) Total Score at Week 78	2.59 Units on a scale Standard Error 0.16	2.44 Units on a scale Standard Error 0.13

Adverse Events

Placebo

Serious events: 77 serious events

Other events: 198 other events

Deaths: 0 deaths

Bapineuzumab

Serious events: 137 serious events

Other events: 298 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=439 participants at risk Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Bapineuzumab n=654 participants at risk Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Blood and lymphatic system disorders Anaemia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Bone marrow failure	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Blood and lymphatic system disorders Leukocytosis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Acute myocardial infarction	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina pectoris	0.46% 2/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Angina unstable	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrioventricular block complete	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Atrioventricular block second degree	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Bradycardia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiac arrest	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Cardiovascular insufficiency	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Hypertensive heart disease	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial infarction	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Myocardial ischaemia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Sinus bradycardia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Supraventricular tachycardia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Cardiac disorders Tachycardia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Cataract	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Eye disorders Vitreous haemorrhage	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Colonic polyp	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Duodenal ulcer perforation	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastric ulcer	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Haematemesis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Ileus	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Inguinal hernia	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Inguinal hernia, obstructive	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Intestinal obstruction	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Nausea	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Vomiting	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest discomfort	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Device occlusion	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Fibrosis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders General physical health deterioration	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Malaise	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Non-cardiac chest pain	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pain	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Bile duct stone	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholangitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholecystitis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Gallbladder disorder	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Jaundice	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Hypersensitivity	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Abdominal abscess	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Abscess	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Appendicitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bacterial Sepsis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Bronchitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Gastroenteritis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Herpes zoster	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Infected skin ulcer	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Kidney infection	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Lower respiratory tract infection	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Meningitis cryptococcal	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Osteomyelitis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Paronychia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.68% 3/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.92% 6/654 • Number of events 6 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pseudomembranous colitis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Sepsis	0.68% 3/439 • Number of events 4 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Toxic shock syndrome	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urosepsis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Vaginitis bacterial	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Viral upper respiratory tract infection	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Accidental overdose	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Contusion	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Drug administration error	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Excoriation	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Eye injury	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Femur fracture	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Head injury	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Hip fracture	0.46% 2/439 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Post lumbar puncture syndrome	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Radius fracture	0.46% 2/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Rib fracture	0.23% 1/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Spinal compression fracture	0.46% 2/439 • Number of events 7 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Stab wound	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Subdural haematoma	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Upper limb fracture	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Wrist fracture	0.46% 2/439 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Blood pressure increased	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Fibrin D dimer increased	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Heart rate increased	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Investigations Streptococcus test positive	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Dehydration	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 4 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Back pain	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lentigo maligna	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm prostate	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.91% 4/439 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.68% 3/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Amyotrophic lateral sclerosis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Aphasia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Brain stem ischaemia	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemorrhage	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral haemosiderin deposition	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral infarction	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral ischaemia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral microhaemorrhage	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.61% 4/654 • Number of events 4 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebrovascular accident	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Convulsion	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Epilepsy	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Grand mal convulsion	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Haemorrhagic stroke	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Hydrocephalus	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Ischaemic stroke	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lacunar infarction	0.23% 1/439 • Number of events 4 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Lethargy	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Loss of consciousness	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Mental impairment	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Paraesthesia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Presyncope	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Syncope	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.61% 4/654 • Number of events 4 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Transient ischaemic attack	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Vasogenic cerebral oedema	0.91% 4/439 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.1% 40/654 • Number of events 61 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Visual field defect	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Abnormal behaviour	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Aggression	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Agitation	0.23% 1/439 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Completed suicide	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Confusional state	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Delirium	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Hallucination	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Mental status changes	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Restlessness	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicide attempt	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Acute prerenal failure	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Haematuria	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Pollakiuria	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure acute	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.31% 2/654 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Breast mass	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Rectocele	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Paranasal cyst	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.23% 1/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.46% 2/439 • Number of events 2 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.46% 3/654 • Number of events 3 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Social circumstances Social problem	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Surgical and medical procedures Thyroidectomy	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Arteriosclerosis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.00% 0/654 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Deep vein thrombosis	0.23% 1/439 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.76% 5/654 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Ischaemia	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Peripheral artery stenosis	0.00% 0/439 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	0.15% 1/654 • Number of events 1 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.

Other adverse events

Measure	Placebo n=439 participants at risk Participants received placebo by intravenous (IV) infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks.	Bapineuzumab n=654 participants at risk Participants received bapineuzumab 0.5 mg/kg by IV infusion every 13 weeks up to 6 doses (65 weeks). Participants were followed up until 78 weeks
Gastrointestinal disorders Diarrhoea	5.2% 23/439 • Number of events 30 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.2% 34/654 • Number of events 38 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Nasopharyngitis	7.7% 34/439 • Number of events 40 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.9% 45/654 • Number of events 66 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Urinary tract infection	5.5% 24/439 • Number of events 37 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.6% 30/654 • Number of events 34 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Fall	6.2% 27/439 • Number of events 36 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.0% 39/654 • Number of events 47 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Cerebral microhaemorrhage	3.6% 16/439 • Number of events 38 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.6% 76/654 • Number of events 218 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Dizziness	5.2% 23/439 • Number of events 32 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	3.1% 20/654 • Number of events 26 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Headache	10.0% 44/439 • Number of events 98 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	6.9% 45/654 • Number of events 66 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Nervous system disorders Vasogenic cerebral oedema	1.1% 5/439 • Number of events 5 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	11.3% 74/654 • Number of events 123 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Anxiety	5.9% 26/439 • Number of events 29 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	4.6% 30/654 • Number of events 61 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Depression	6.2% 27/439 • Number of events 73 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	5.4% 35/654 • Number of events 95 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypertension	5.0% 22/439 • Number of events 50 • 4 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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.	2.8% 18/654 • Number of events 48 • 4 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 participant and as nonserious in another participant, or one participant 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