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Clinical Trial Results:
A Multicenter, Open-label, Single-arm, Extension Study to Assess Long-term Safety of Evolocumab Therapy in Subjects With Clinically Evident Cardiovascular Disease in Selected European Countries

Summary
EudraCT number	2016-004066-26
Trial protocol	DE SE DK PT BE IT
Global end of trial date	04 Mar 2022

Results information
Results version number	v1(current)
This version publication date	05 Jan 2023
First version publication date	05 Jan 2023
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

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Sponsor protocol code

20160250

ISRCTN number

-

US NCT number

NCT03080935

WHO universal trial number (UTN)

-

Sponsor organisation name

Amgen Inc.

Sponsor organisation address

One Amgen Center Drive, Thousand Oaks, CA, United States,

Public contact

Amgen (EUROPE) GmbH, IHQ Medical Info-Clinical Trials, MedInfoInternational@amgen.com

Scientific contact

Amgen (EUROPE) GmbH, IHQ Medical Info-Clinical Trials, MedInfoInternational@amgen.com

Is trial part of an agreed paediatric investigation plan (PIP)

No

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

No

Analysis stage

Final

Date of interim/final analysis

04 Mar 2022

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

04 Mar 2022

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of this trial was to describe the safety and tolerability of long-term administration of evolocumab.

Protection of trial subjects

This study was conducted in accordance with International Council on Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines.

Background therapy

-

Evidence for comparator

-

Actual start date of recruitment

13 Mar 2017

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

No

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 158

Country: Number of subjects enrolled

Denmark: 354

Country: Number of subjects enrolled

France: 178

Country: Number of subjects enrolled

Germany: 292

Country: Number of subjects enrolled

Italy: 198

Country: Number of subjects enrolled

Portugal: 191

Country: Number of subjects enrolled

Sweden: 229

Worldwide total number of subjects

1600

EEA total number of subjects

1600

Number of subjects enrolled per age group

In utero

0

Preterm newborn - gestational age < 37 wk

0

Newborns (0-27 days)

0

Infants and toddlers (28 days-23 months)

0

Children (2-11 years)

0

Adolescents (12-17 years)

0

Adults (18-64 years)

823

From 65 to 84 years

776

85 years and over

1

Subject disposition

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Recruitment details

This was an open-label extension of study 20110118 (NCT01764633). Eligible participants were enrolled after the completion of the 20110118 study. Participants were enrolled at 86 centers in Belgium, Germany, Denmark, France, Italy, Portugal, and Sweden.

Screening details

Participants were enrolled from 13 March 2017 to 04 March 2022. A total of 1600 participants were enrolled and 1599 of those participants received study drug.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo in Parent Study

Arm description

Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

Other name

Repatha

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Evolocumab was administered by subcutaneous injections either 140 mg every 2 weeks or 420 mg monthly, according to the participant's preference.

Evolocumab in Parent Study

Arm description

Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

Arm type

Experimental

Investigational medicinal product name

Evolocumab

Investigational medicinal product code

Other name

Repatha

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Evolocumab was administered by subcutaneous injections either 140 mg every 2 weeks or 420 mg monthly, according to the participant's preference.

Number of subjects in period 1	Placebo in Parent Study	Evolocumab in Parent Study
Started	745	855
Completed	695	786
Not completed	50	69
Adverse event, serious fatal	34	50
Consent withdrawn by subject	11	15
Lost to follow-up	5	4

Baseline characteristics

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Reporting group title

Placebo in Parent Study

Reporting group description

Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

Reporting group title

Evolocumab in Parent Study

Reporting group description

Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

Reporting group values	Placebo in Parent Study	Evolocumab in Parent Study	Total
Number of subjects	745	855	1600
Age Categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	378	444	822
From 65-84 years	367	409	776
85 years and over	0	1	1
Unknown	0	1	1
Gender Categorical
Units: Subjects
Female	138	151	289
Male	607	703	1310
Unknown	0	1	1
Ethnicity
Units: Subjects
Hispanic/Latino	17	24	41
Not Hispanic/Latino	728	830	1558
Unknown	0	1	1
Race
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	0	2	2
Black or African American	1	0	1
Native Hawaiian or Other Pacific Islander	0	2	2
White	706	797	1503
Multiple	0	0	0
Other	38	53	91
Unknown	0	1	1

End points

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Reporting group title

Placebo in Parent Study

Reporting group description

Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

Reporting group title

Evolocumab in Parent Study

Reporting group description

Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

Primary: Number of Participants Who Experienced an Adverse Event (AE)

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End point title

Number of Participants Who Experienced an Adverse Event (AE) ^[1]

End point description

All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.

End point type

Primary

End point timeframe

Up to 5 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis was planned for this endpoint.

End point values	Placebo in Parent Study	Evolocumab in Parent Study
Number of subjects analysed	745	854
Units: Participants
Number of Participants Who Experienced an AE	686	810

No statistical analyses for this end point

Secondary: Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit

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End point title

Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit

End point description

End point type

Secondary

End point timeframe

Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260

End point values	Placebo in Parent Study	Evolocumab in Parent Study
Number of subjects analysed	745	854
Units: Percent Change
arithmetic mean (standard deviation)
Week 12	-66.32 ± 26.88	-67.24 ± 25.23
Week 24	-66.48 ± 27.52	-66.47 ± 28.11
Week 48	-62.61 ± 26.60	-63.45 ± 26.03
Week 72	-65.58 ± 28.13	-65.33 ± 28.42
Week 96	-64.58 ± 27.01	-63.43 ± 28.80
Week 120	-64.26 ± 28.31	-63.10 ± 29.56
Week 144	-66.79 ± 29.22	-65.13 ± 31.96
Week 168	-65.28 ± 27.55	-63.55 ± 29.60
Week 192	-65.02 ± 27.93	-62.46 ± 26.39
Week 216	-64.92 ± 27.93	-62.46 ± 28.32
Week 260	-66.45 ± 29.84	-64.72 ± 29.50

No statistical analyses for this end point

Secondary: Percentage of Participants who Achieved an LDL-C level < 40 mg/dL

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End point title

Percentage of Participants who Achieved an LDL-C level < 40 mg/dL

End point description

End point type

Secondary

End point timeframe

Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260

End point values	Placebo in Parent Study	Evolocumab in Parent Study
Number of subjects analysed	745	854
Units: Percentage of Participants
number (confidence interval 95%)
Week 12	72.8 (69.4 to 75.9)	72.5 (69.4 to 75.4)
Week 24	72.9 (69.5 to 76.0)	73.4 (70.3 to 76.2)
Week 48	66.5 (63.0 to 69.9)	68.0 (64.8 to 71.1)
Week 72	73.2 (69.8 to 76.3)	72.3 (69.1 to 75.2)
Week 96	71.1 (67.6 to 74.3)	69.2 (65.9 to 72.3)
Week 120	70.9 (67.5 to 74.2)	68.6 (65.3 to 71.8)
Week 144	75.3 (71.2 to 78.9)	72.2 (68.5 to 75.7)
Week 168	72.3 (68.8 to 75.6)	69.3 (65.9 to 72.5)
Week 192	71.6 (67.9 to 74.9)	66.3 (62.8 to 69.7)
Week 216	72.1 (68.6 to 75.4)	67.3 (63.9 to 70.6)
Week 260	76.1 (71.6 to 80.2)	68.8 (64.2 to 73.0)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to 5 years

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Placebo in Parent Study

Reporting group description

Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference.

Reporting group title

Evolocumab in Parent Study

Reporting group description

Participants in the parent study who received evolocumab either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participants preference.

Serious adverse events	Placebo in Parent Study	Evolocumab in Parent Study
Total subjects affected by serious adverse events
subjects affected / exposed	323 / 745 (43.36%)	410 / 854 (48.01%)
number of deaths (all causes)	35	51
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Angiosarcoma metastatic
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Adenocarcinoma pancreas
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Basal cell carcinoma
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Benign neoplasm of thyroid gland
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Benign anorectal neoplasm
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Bladder cancer recurrent
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder cancer stage III
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder transitional cell carcinoma recurrent
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bladder transitional cell carcinoma stage I
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Brain cancer metastatic
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial carcinoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Brain neoplasm malignant
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Breast cancer male
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chromophobe renal cell carcinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cancer fatigue
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangiocarcinoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Colon adenoma
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer stage I
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enchondromatosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal neoplasm
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colon cancer stage III
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal cancer
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Glioblastoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lentigo maligna stage I
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Laryngeal squamous cell carcinoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Glioblastoma multiforme
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Lung cancer metastatic
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1
Lung carcinoma cell type unspecified stage IV
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	3 / 745 (0.40%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Lung adenocarcinoma stage I
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lung squamous cell carcinoma metastatic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Malignant melanoma
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant neoplasm of unknown primary site
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Malignant palate neoplasm
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphangiosis carcinomatosa
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meningioma benign
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to bone
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to central nervous system
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to lung
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastases to lymph nodes
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metastatic gastric cancer
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metastatic squamous cell carcinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal neoplasm benign
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neuroendocrine tumour of the lung
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Non-small cell lung cancer
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Oropharyngeal squamous cell carcinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Non-small cell lung cancer stage IV
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Non-small cell lung cancer metastatic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancoast's tumour
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Ovarian adenoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic carcinoma metastatic
subjects affected / exposed	0 / 745 (0.00%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 4
Pituitary tumour
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	0 / 745 (0.00%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1
Plasma cell myeloma
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural mesothelioma malignant
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural neoplasm
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	6 / 745 (0.81%)	7 / 854 (0.82%)
occurrences causally related to treatment / all	0 / 6	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 1
Prostate cancer metastatic
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer stage I
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostate cancer stage II
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatic adenoma
subjects affected / exposed	1 / 745 (0.13%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0
Renal cancer
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal cell carcinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Richter's syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal neoplasm
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin angiosarcoma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Small intestine carcinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Small intestine carcinoma stage IV
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Squamous cell carcinoma of skin
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transitional cell cancer of the renal pelvis and ureter
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic aneurysm
subjects affected / exposed	4 / 745 (0.54%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 4	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Arterial stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriosclerosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Femoral artery aneurysm
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Extremity necrosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertension
subjects affected / exposed	4 / 745 (0.54%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Haematoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Iliac artery occlusion
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypotension
subjects affected / exposed	4 / 745 (0.54%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Iliac artery stenosis
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Intermittent claudication
subjects affected / exposed	3 / 745 (0.40%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic limb pain
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphocele
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	12 / 745 (1.61%)	12 / 854 (1.41%)
occurrences causally related to treatment / all	0 / 13	0 / 24
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery occlusion
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery aneurysm
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	4 / 745 (0.54%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 5	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	3 / 745 (0.40%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	1 / 745 (0.13%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 1	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral vein stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subclavian vein thrombosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pain
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Venous thrombosis limb
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Coronary revascularisation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Implantable defibrillator insertion
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Knee arthroplasty
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileectomy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin neoplasm excision
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve repair
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
subjects affected / exposed	4 / 745 (0.54%)	7 / 854 (0.82%)
occurrences causally related to treatment / all	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Death
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Disease progression
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Fibrosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fatigue
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Incarcerated hernia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inflammation
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Malaise
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple organ dysfunction syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Necrosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	3 / 745 (0.40%)	10 / 854 (1.17%)
occurrences causally related to treatment / all	0 / 4	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Oedema peripheral
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Stent-graft endoleak
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden cardiac death
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Sudden death
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 2
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Unevaluable event
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent occlusion
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent stenosis
subjects affected / exposed	3 / 745 (0.40%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular stent thrombosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Endometrial hyperplasia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Benign prostatic hyperplasia
subjects affected / exposed	4 / 745 (0.54%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Genital prolapse
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gynaecomastia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatomegaly
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	3 / 745 (0.40%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory distress syndrome
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Acute respiratory failure
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Asthma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis chronic
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	7 / 745 (0.94%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 8	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diaphragmatic paralysis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity pneumonitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal obstruction
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lung disorder
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal polyps
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nasal turbinate hypertrophy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pickwickian syndrome
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax spontaneous
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pleurisy
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary granuloma
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	3 / 745 (0.40%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	2 / 745 (0.27%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Alcohol abuse
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Confusional state
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Alcoholism
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Depression
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Eating disorder
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hallucination, auditory
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hallucination
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Insomnia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric decompensation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Product issues
Device dislocation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device occlusion
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device physical property issue
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Device material issue
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Device power source issue
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Biliary polyp
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	2 / 745 (0.27%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis acute
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	4 / 745 (0.54%)	9 / 854 (1.05%)
occurrences causally related to treatment / all	0 / 4	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis obstructive
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	4 / 745 (0.54%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Blood creatinine increased
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Blood pressure orthostatic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
C-reactive protein increased
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac function test abnormal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Echocardiogram abnormal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ejection fraction decreased
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
International normalised ratio abnormal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oxygen saturation abnormal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Transvalvular pressure gradient increased
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
SARS-CoV-2 antibody test positive
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Abdominal injury
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Accidental overdose
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ankle fracture
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Alcohol poisoning
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriovenous fistula thrombosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervical vertebral fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chest injury
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Clavicle fracture
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Contusion
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Comminuted fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Electric injury
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 745 (0.00%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery restenosis
subjects affected / exposed	3 / 745 (0.40%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	3 / 745 (0.40%)	6 / 854 (0.70%)
occurrences causally related to treatment / all	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 0
Femoral neck fracture
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	3 / 745 (0.40%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Fractured sacrum
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria traumatic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hip fracture
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hyphaema
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Joint dislocation postoperative
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Limb traumatic amputation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Medical device monitoring error
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar vertebral fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle rupture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle contusion
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haematoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumothorax traumatic
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Patella fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haematuria
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural swelling
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Postpericardiotomy syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural pain
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Procedural pneumothorax
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Restenosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Scapula fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Scratch
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Seroma
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Skin injury
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin wound
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal compression fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon rupture
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
Splinter
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Thoracic vertebral fracture
subjects affected / exposed	0 / 745 (0.00%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic arthrosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic haematoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular access site haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft occlusion
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular anastomosis aneurysm
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular pseudoaneurysm
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular graft thrombosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound complication
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Wound haemorrhage
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Atrial septal defect
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyloric stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Von Hippel-Lindau disease
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	4 / 745 (0.54%)	7 / 854 (0.82%)
occurrences causally related to treatment / all	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Acute myocardial infarction
subjects affected / exposed	18 / 745 (2.42%)	15 / 854 (1.76%)
occurrences causally related to treatment / all	0 / 19	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	26 / 745 (3.49%)	24 / 854 (2.81%)
occurrences causally related to treatment / all	0 / 31	0 / 28
deaths causally related to treatment / all	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	15 / 745 (2.01%)	13 / 854 (1.52%)
occurrences causally related to treatment / all	0 / 19	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve calcification
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve incompetence
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	15 / 745 (2.01%)	22 / 854 (2.58%)
occurrences causally related to treatment / all	0 / 19	0 / 28
deaths causally related to treatment / all	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	2 / 745 (0.27%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Bundle branch block left
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure
subjects affected / exposed	17 / 745 (2.28%)	27 / 854 (3.16%)
occurrences causally related to treatment / all	0 / 25	0 / 38
deaths causally related to treatment / all	0 / 1	0 / 3
Cardiac failure acute
subjects affected / exposed	2 / 745 (0.27%)	6 / 854 (0.70%)
occurrences causally related to treatment / all	0 / 2	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac failure chronic
subjects affected / exposed	6 / 745 (0.81%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 6	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac valve disease
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardio-respiratory arrest
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Cardiogenic shock
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiorenal syndrome
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	6 / 745 (0.81%)	10 / 854 (1.17%)
occurrences causally related to treatment / all	0 / 6	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic coronary syndrome
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congestive cardiomyopathy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery occlusion
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	5 / 745 (0.67%)	11 / 854 (1.29%)
occurrences causally related to treatment / all	0 / 6	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary artery thrombosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coronary ostial stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dressler's syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Extrasystoles
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular failure
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular hypertrophy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Left ventricular dysfunction
subjects affected / exposed	3 / 745 (0.40%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Low cardiac output syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve incompetence
subjects affected / exposed	1 / 745 (0.13%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Mitral valve stenosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Palpitations
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	7 / 745 (0.94%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0
Myocardial infarction
subjects affected / exposed	6 / 745 (0.81%)	9 / 854 (1.05%)
occurrences causally related to treatment / all	0 / 6	0 / 10
deaths causally related to treatment / all	0 / 2	0 / 2
Pericardial effusion
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinoatrial block
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus bradycardia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular extrasystoles
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tricuspid valve incompetence
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	8 / 745 (1.07%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 10	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	3 / 745 (0.40%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Carotid artery stenosis
subjects affected / exposed	3 / 745 (0.40%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral artery embolism
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Carotid arteriosclerosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Amputation stump pain
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral atrophy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	4 / 745 (0.54%)	6 / 854 (0.70%)
occurrences causally related to treatment / all	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 1
Cerebral thrombosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Dementia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cervicobrachial syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Coma
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dementia with Lewy bodies
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dizziness
subjects affected / exposed	3 / 745 (0.40%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Essential tremor
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Dysaesthesia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Embolic stroke
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intraventricular haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic cerebral infarction
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	8 / 745 (1.07%)	14 / 854 (1.64%)
occurrences causally related to treatment / all	0 / 9	1 / 16
deaths causally related to treatment / all	0 / 1	0 / 1
Memory impairment
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nerve compression
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Normal pressure hydrocephalus
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peripheral nerve lesion
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Piriformis syndrome
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Post-traumatic headache
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatic nerve neuropathy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sciatica
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Seizure
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	10 / 745 (1.34%)	10 / 854 (1.17%)
occurrences causally related to treatment / all	0 / 10	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Transient global amnesia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	9 / 745 (1.21%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 9	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
VIth nerve paralysis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Coagulopathy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Autoimmune haemolytic anaemia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Anaemia
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Microcytic anaemia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haemorrhagic disorder
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Necrotic lymphadenopathy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Normochromic normocytic anaemia
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ear and labyrinth disorders
Meniere's disease
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sudden hearing loss
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	0 / 745 (0.00%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Blepharitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blindness
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Corneal oedema
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diplopia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Keratopathy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lens dislocation
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Visual impairment
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 745 (0.13%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis ulcerative
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis microscopic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dental caries
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulum intestinal haemorrhagic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Enlarged uvula
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric cyst
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric polyps
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric ulcer haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gastrointestinal ulcer
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal vascular malformation haemorrhagic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intestinal polyp
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar hernia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Melaena
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Oedematous pancreatitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatic cyst
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritoneal haematoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rectal polyp
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Volvulus of small bowel
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic foot
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prurigo
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pruritus
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypertrichosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ischaemic skin ulcer
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin necrosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Calculus bladder
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Calculus urethral
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	6 / 745 (0.81%)	8 / 854 (0.94%)
occurrences causally related to treatment / all	0 / 7	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0
Haematuria
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis noninfective
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Micturition disorder
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	4 / 745 (0.54%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 4	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Nephropathy
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ureteric stenosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Paroxysmal nocturnal haemoglobinuria
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Urethral obstruction
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary bladder polyp
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinoma
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Adrenal haemorrhage
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Chondrocalcinosis pyrophosphate
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bursitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Compartment syndrome
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Exostosis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haematoma muscle
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Inclusion body myositis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc compression
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc degeneration
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc disorder
subjects affected / exposed	1 / 745 (0.13%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	3 / 745 (0.40%)	6 / 854 (0.70%)
occurrences causally related to treatment / all	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Lumbar spinal stenosis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Muscle spasms
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Myalgia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Neck pain
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Osteitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	8 / 745 (1.07%)	15 / 854 (1.76%)
occurrences causally related to treatment / all	0 / 8	0 / 18
deaths causally related to treatment / all	0 / 0	0 / 0
Osteochondrosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Patellofemoral pain syndrome
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psoriatic arthropathy
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Polymyalgia rheumatica
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	7 / 745 (0.94%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 7	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Synovitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon disorder
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Tendon pain
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 745 (0.13%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Abscess jaw
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal abscess
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19
subjects affected / exposed	6 / 745 (0.81%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Bronchitis
subjects affected / exposed	0 / 745 (0.00%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Campylobacter gastroenteritis
subjects affected / exposed	2 / 745 (0.27%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 745 (0.00%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cystitis
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Dermo-hypodermitis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Diverticulitis intestinal haemorrhagic
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Empyema
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	7 / 745 (0.94%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 7	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 745 (0.13%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis bacterial
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatitis A
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster cutaneous disseminated
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 745 (0.13%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1
Infectious pleural effusion
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	3 / 745 (0.40%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Liver abscess
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphangitis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Localised infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nasopharyngitis
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis streptococcal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Mediastinal abscess
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oral infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	15 / 745 (2.01%)	19 / 854 (2.22%)
occurrences causally related to treatment / all	0 / 17	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 1
Pneumonia aspiration
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	3 / 745 (0.40%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia mycoplasmal
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Prostatitis Escherichia coli
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Pyelonephritis
subjects affected / exposed	0 / 745 (0.00%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	3 / 745 (0.40%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Septic embolus
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	4 / 745 (0.54%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatococcal infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tracheobronchitis
subjects affected / exposed	0 / 745 (0.00%)	3 / 854 (0.35%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	4 / 745 (0.54%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1
Urosepsis
subjects affected / exposed	3 / 745 (0.40%)	4 / 854 (0.47%)
occurrences causally related to treatment / all	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1
Vascular device infection
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	3 / 745 (0.40%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Abnormal loss of weight
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	2 / 745 (0.27%)	5 / 854 (0.59%)
occurrences causally related to treatment / all	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetes mellitus inadequate control
subjects affected / exposed	3 / 745 (0.40%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diabetic ketoacidosis
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Electrolyte imbalance
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Folate deficiency
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gout
subjects affected / exposed	1 / 745 (0.13%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	2 / 745 (0.27%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	2 / 745 (0.27%)	2 / 854 (0.23%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Hypokalaemia
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Obesity
subjects affected / exposed	2 / 745 (0.27%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Overweight
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Steroid diabetes
subjects affected / exposed	1 / 745 (0.13%)	0 / 854 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	0 / 745 (0.00%)	1 / 854 (0.12%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo in Parent Study	Evolocumab in Parent Study
Total subjects affected by non serious adverse events
subjects affected / exposed	451 / 745 (60.54%)	528 / 854 (61.83%)
Vascular disorders
Hypertension
subjects affected / exposed	132 / 745 (17.72%)	150 / 854 (17.56%)
occurrences all number	159	179
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	37 / 745 (4.97%)	49 / 854 (5.74%)
occurrences all number	39	55
Nervous system disorders
Dizziness
subjects affected / exposed	33 / 745 (4.43%)	43 / 854 (5.04%)
occurrences all number	38	50
General disorders and administration site conditions
Chest pain
subjects affected / exposed	40 / 745 (5.37%)	29 / 854 (3.40%)
occurrences all number	45	34
Eye disorders
Cataract
subjects affected / exposed	42 / 745 (5.64%)	32 / 854 (3.75%)
occurrences all number	49	43
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	39 / 745 (5.23%)	40 / 854 (4.68%)
occurrences all number	42	44
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	61 / 745 (8.19%)	75 / 854 (8.78%)
occurrences all number	77	87
Back pain
subjects affected / exposed	50 / 745 (6.71%)	70 / 854 (8.20%)
occurrences all number	55	80
Myalgia
subjects affected / exposed	55 / 745 (7.38%)	47 / 854 (5.50%)
occurrences all number	60	55
Pain in extremity
subjects affected / exposed	24 / 745 (3.22%)	50 / 854 (5.85%)
occurrences all number	27	55
Infections and infestations
Pneumonia
subjects affected / exposed	42 / 745 (5.64%)	41 / 854 (4.80%)
occurrences all number	47	57
Nasopharyngitis
subjects affected / exposed	75 / 745 (10.07%)	111 / 854 (13.00%)
occurrences all number	97	155
Influenza
subjects affected / exposed	37 / 745 (4.97%)	53 / 854 (6.21%)
occurrences all number	37	56
Bronchitis
subjects affected / exposed	32 / 745 (4.30%)	43 / 854 (5.04%)
occurrences all number	49	55
Metabolism and nutrition disorders
Diabetes mellitus
subjects affected / exposed	60 / 745 (8.05%)	57 / 854 (6.67%)
occurrences all number	61	61

More information

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Were there any global substantial amendments to the protocol? Yes

14 Dec 2018

The protocol was amended for the following reasons: • Financial disclosure statement text was removed as this was not applicable to this study (only European sites were participating). • An independent external CEC was established and reviewed deaths and cardiovascular events of interest; cardiovascular events of interest to be reviewed were defined. • The term “targeted” concomitant therapy was removed throughout; all concomitant therapy was assessed. • Statistical considerations were clarified to include that the primary analysis of all endpoints in the OLE study will only use OLE study data and how CEC events were analyzed. • Exposure time intervals were modified. • The text was clarified to indicate that the lipid profiles are conducted at scheduled visits and not on a yearly basis and week 260 was removed as part of end of study definition. • The information collected for concomitant therapy for disease under study, antibiotics, and then all other therapies was clarified. • Male contraception language removed as not applicable. • Clarification of how data were collected and defined when a subject transitions from parent to OLE study, including medical history and what data were transferred to OLE study was added. • Redundant text for subject withdrawal and concomitant therapy was removed. • The resupply period was clarified. • Lot number was changed to box number for accuracy. • Lost to follow-up section was added for clarity.

19 Feb 2020

The protocol was amended for the following reasons: • The safety section was updated to reflect that all serious drug-related events must be recorded and reported to the sponsor or designee within 24 hours. • “Coronary revascularization” was included throughout the protocol to identify the specific vascular territory of interest, which is the coronary circulation. • The identified Events of Interest (EOIs) were removed from the protocol and are no longer prespecified. • Week 260 was added back into the schedule of assessments to realign with the 20130295 sister study. • Coronary revascularization procedure and death information was added throughout to support the independent safety review of cardiovascular EOIs and deaths by the CEC. • Dosing details were clarified including details regarding the switch frequency between AI/pen and personal injector were added, and the last resupply of evolocumab will occur 12 weeks after the week 240 visit. • Updated the exploratory objectives to be consistent with exploratory endpoints. • Remove language in the definition of Primary Completion to align with current protocol template.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

This study was terminated to coincide with the completion of study 20130295 (NCT02867813). The study was not terminated due to any safety findings.

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