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The European Union Clinical Trials Register allows you to search for protocol and results information on:

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Clinical Trial Results:
Efficacy and Safety Study of Darolutamide (ODM-201) in Men With High-risk Non-metastatic Castration-resistant Prostate Cancer (ARAMIS)

Summary
EudraCT number	2013-003820-36
Trial protocol	SE HU FI LV CZ AT GB SK DE PT IT BE BG FR PL RO LT EE
Global end of trial date	14 Jun 2021

Results information
Results version number	v1(current)
This version publication date	18 Jun 2022
First version publication date	18 Jun 2022
Other versions

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

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Trial information

Top of page

Sponsor protocol code

17712

ISRCTN number

-

US NCT number

NCT02200614

WHO universal trial number (UTN)

-

Sponsor organisation name

Bayer AG

Sponsor organisation address

Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368

Public contact

Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.com

Scientific contact

Therapeutic Area Head, Bayer AG, +49 30 300139003, clinical-trials-contact@bayer.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

14 Jun 2021

Is this the analysis of the primary completion data?

No

Global end of trial reached?

Yes

Global end of trial date

14 Jun 2021

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of this study was to demonstrate the superiority of darolutamide vs. placebo in metastasis-free survival (MFS), in patients with high-risk nmCRPC.

Protection of trial subjects

The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent was read by and explained to all the subjects. Participating subjects signed the informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.

Background therapy

Androgen deprivation therapy (ADT)

Evidence for comparator

-

Actual start date of recruitment

12 Sep 2014

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Austria: 6

Country: Number of subjects enrolled

Estonia: 5

Country: Number of subjects enrolled

Finland: 45

Country: Number of subjects enrolled

France: 80

Country: Number of subjects enrolled

Latvia: 62

Country: Number of subjects enrolled

Lithuania: 79

Country: Number of subjects enrolled

Poland: 33

Country: Number of subjects enrolled

Sweden: 22

Country: Number of subjects enrolled

Argentina: 5

Country: Number of subjects enrolled

Australia: 21

Country: Number of subjects enrolled

Brazil: 100

Country: Number of subjects enrolled

Canada: 45

Country: Number of subjects enrolled

Colombia: 7

Country: Number of subjects enrolled

Israel: 1

Country: Number of subjects enrolled

Japan: 95

Country: Number of subjects enrolled

Korea, Republic of: 76

Country: Number of subjects enrolled

Peru: 22

Country: Number of subjects enrolled

South Africa: 16

Country: Number of subjects enrolled

Taiwan: 15

Country: Number of subjects enrolled

United States: 139

Country: Number of subjects enrolled

Czechia: 29

Country: Number of subjects enrolled

Germany: 62

Country: Number of subjects enrolled

Italy: 30

Country: Number of subjects enrolled

Bulgaria: 2

Country: Number of subjects enrolled

Romania: 28

Country: Number of subjects enrolled

Spain: 117

Country: Number of subjects enrolled

Belarus: 31

Country: Number of subjects enrolled

Belgium: 15

Country: Number of subjects enrolled

Hungary: 28

Country: Number of subjects enrolled

Portugal: 36

Country: Number of subjects enrolled

Russian Federation: 105

Country: Number of subjects enrolled

Serbia: 8

Country: Number of subjects enrolled

Slovakia: 13

Country: Number of subjects enrolled

Turkey: 27

Country: Number of subjects enrolled

Ukraine: 56

Country: Number of subjects enrolled

United Kingdom: 48

Worldwide total number of subjects

1509

EEA total number of subjects

692

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)

197

From 65 to 84 years

1182

85 years and over

130

Subject disposition

Top of page

Recruitment details

Study was conducted at multiple centers in 36 countries between 12 September 2014 (first subject first visit) and 14 June 2021 (last subject last visit).

Screening details

From 2696 subjects who signed informed consent, 1187 subjects were discontinued from screening. A total of 1509 subjects were randomly assigned to either darolutamide arm or placebo arm. The study was unblinded on 30 OCT 2018 and subjects in the placebo arm could cross over to open-label darolutamide treatment.

Period 1 title

Double blind treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Darolutamide (BAY1841788)

Arm description

Subjects received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Arm type

Experimental

Investigational medicinal product name

Darolutamide

Investigational medicinal product code

BAY1841788

Other name

ODM-201

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

600 mg (2 tablets of 300 mg) b.i.d. with food, equal to a total daily dose of 1200 mg

Placebo

Arm description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Arm type

Active comparator

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets twice daily with food

Number of subjects in period 1	Darolutamide (BAY1841788)	Placebo
Started	955	554
Completed	591	170
Not completed	364	384
Confirmed metastasis	120	140
Personal reason	77	85
Judgment of the investigator	59	99
Protocol deviation	14	7
Adverse event	86	48
Other reason	6	2
Metastasis by local reading	1	3
Not treated	1	-

Period 2 title

Open label

Is this the baseline period?

No

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Darolutamide (BAY1841788)

Arm description

Subjects received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Arm type

Experimental

Investigational medicinal product name

Darolutamide

Investigational medicinal product code

BAY1841788

Other name

ODM-201

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

600 mg (2 tablets of 300 mg) b.i.d. with food, equal to a total daily dose of 1200 mg

Placebo

Arm description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

2 tablets twice daily with food

Number of subjects in period 2	Darolutamide (BAY1841788)	Placebo
Started	591	170
Completed	295	114
Not completed	296	56
Confirmed metastasis	1	-
Personal reason	60	8
Judgment of the investigator	29	2
Protocol deviation	3	2
Adverse event	41	11
Other reason	22	4
Metastasis by local reading	138	27
Missing	2	2

Baseline characteristics

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Reporting group title

Darolutamide (BAY1841788)

Reporting group description

Subjects received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Reporting group title

Placebo

Reporting group description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Reporting group values	Darolutamide (BAY1841788)	Placebo	Total
Number of subjects	955	554	1509
Age categorical
Units: Subjects
Age Continuous
Units: years
arithmetic mean (standard deviation)	73.9 ( 7.8 )	73.2 ( 8.2 )	-
Sex: Female, Male
Units: participants
Female	0	0	0
Male	955	554	1509
Race/Ethnicity, Customized
Units: Subjects
Asia	122	71	193
Black or African American	28	24	52
White	760	434	1194
Missing	36	19	55
Other	9	6	15

End points

Top of page

Reporting group title

Darolutamide (BAY1841788)

Reporting group description

Subjects received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Reporting group title

Placebo

Reporting group description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Reporting group title

Darolutamide (BAY1841788)

Reporting group description

Subjects received Darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Reporting group title

Placebo

Reporting group description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Primary: Metastasis-Free Survival

Top of page

End point title

Metastasis-Free Survival

End point description

Metastasis-Free Survival (MFS) is defined as the time from randomisation to evidence of metastasis or death from any cause, whichever occurs first (cut-off date 15 Nov 2019). 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Primary

End point timeframe

From randomization to the time approximately 385 MFS events were observed (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	40.37 (34.33 to 99999)	18.43 (15.51 to 22.34)

Metastasis-Free Survival

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[1]

P-value

< 0.000001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.413

Confidence interval

level

95%

sides

2-sided

lower limit

0.341

upper limit

0.5

Notes
[1] - Hazard ratio and 95% Confidence Interval (CI) was based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Overall Survival - Primary analysis

Top of page

End point title

Overall Survival - Primary analysis

End point description

Overall Survival (OS) was defined as the time from randomization to death due to any cause. 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization of the first subject to the time approximatively 140 death events were observed (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (44.45 to 99999)	99999 (99999 to 99999)

Overall Survival

Statistical analysis description

Primary analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.04521

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.706

Confidence interval

level

95%

sides

2-sided

lower limit

0.501

upper limit

0.994

Notes
[2] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to pain progression - Primary analysis

Top of page

End point title

Time to pain progression - Primary analysis

End point description

Time to pain progression (PP) is defined as time from randomization to pain progression, where progression is defined as an increase of 2 or more points from baseline in question 3 of the Brief Pain Inventory-Short Form questionnaire (BPI-SF) related to the worst pain in the last 24 hours taken as a 7-day average for post-baseline scores, or initiation of short or long-acting opioids for pain, whichever comes first. Initiation or change in the use of other non-opioid analgesics is not used in the analysis of pain progression.

End point type

Secondary

End point timeframe

From randomization until last study treatment (assessed every 4 months) (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	40.31 (33.21 to 41.20)	25.36 (19.09 to 29.63)

Time to pain progression

Statistical analysis description

Primary analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.000008

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.647

Confidence interval

level

95%

sides

2-sided

lower limit

0.533

upper limit

0.785

Notes
[3] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to initiation of first cytotoxic chemotherapy for prostate cancer - Primary analysis

Top of page

End point title

Time to initiation of first cytotoxic chemotherapy for prostate cancer - Primary analysis

End point description

The time to cytotoxic chemotherapy was defined as the time from randomization to the start of the first cytotoxic chemotherapy cycle. 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization until last study treatment (assessed every 4 months) (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	38.21 (35.55 to 41.89)

Time to initiation of first cytotoxic chemotherapy

Statistical analysis description

Primary analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

< 0.000001

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.433

Confidence interval

level

95%

sides

2-sided

lower limit

0.314

upper limit

0.595

Notes
[4] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to first symptomatic skeletal event (SSE) - Primary analysis

Top of page

End point title

Time to first symptomatic skeletal event (SSE) - Primary analysis

End point description

The time to the first SSE was defined as the time from randomization to the occurrence of the first SSE. 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization until last study treatment (assessed every 4 months) (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Time to first SSE

Statistical analysis description

Primary analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[5]

P-value

= 0.011262

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.428

Confidence interval

level

95%

sides

2-sided

lower limit

0.218

upper limit

0.842

Notes
[5] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Overall Survival - Final analysis

Top of page

End point title

Overall Survival - Final analysis

End point description

Overall Survival (OS) was defined as the time from randomization to death due to any cause. The final analysis was done at the time of the data cut-off (15 NOV 2019). 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization of the first subject to the time approximatively 254 death events were observed (approximately 56 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (56.14 to 99999)	99999 (46.91 to 99999)

Overall Survival

Statistical analysis description

Final analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[6]

P-value

= 0.003048

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.685

Confidence interval

level

95%

sides

2-sided

lower limit

0.533

upper limit

0.881

Notes
[6] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to pain progression - Final analysis

Top of page

End point title

Time to pain progression - Final analysis

End point description

For time to pain progression, the analysis performed using the primary completion cut-off data (03 SEP 2018) was considered final and no new analysis was performed for time to pain progression.

End point type

Secondary

End point timeframe

From randomization until last study treatment (assessed every 4 months) (approximately 48 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	40.31 (33.21 to 41.20)	25.36 (19.09 to 29.63)

Time to pain progression

Statistical analysis description

Final analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[7]

P-value

= 0.000008

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.647

Confidence interval

level

95%

sides

2-sided

lower limit

0.533

upper limit

0.785

Notes
[7] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to initiation of first cytotoxic chemotherapy for prostate cancer - Final analysis

Top of page

End point title

Time to initiation of first cytotoxic chemotherapy for prostate cancer - Final analysis

End point description

The time to cytotoxic chemotherapy was defined as the time from randomization to the start of the first cytotoxic chemotherapy cycle. The final analysis was done at the time of the data cut-off (15 NOV 2019). 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization until initiation of first cytotoxic chemotherapy treatment (approximately 59 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Time to initiation of first cytotoxic chemotherapy

Statistical analysis description

Final analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[8]

P-value

= 0.000044

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.579

Confidence interval

level

95%

sides

2-sided

lower limit

0.444

upper limit

0.755

Notes
[8] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Secondary: Time to first symptomatic skeletal event (SSE) - Final analysis

Top of page

End point title

Time to first symptomatic skeletal event (SSE) - Final analysis

End point description

The time to the first SSE was defined as the time from randomization to the occurrence of the first SSE. The final analysis was done at the time of the data cut-off (15 NOV 2019). 99999 = value cannot be estimated due to censored data, insufficient number of subjects with events.

End point type

Secondary

End point timeframe

From randomization until occurrence of first SSE event (approximately 59 months)

End point values	Darolutamide (BAY1841788)	Placebo
Number of subjects analysed	955	554
Units: months
median (confidence interval 95%)	99999 (99999 to 99999)	99999 (99999 to 99999)

Time to first SSE

Statistical analysis description

Final analysis

Comparison groups

Darolutamide (BAY1841788) v Placebo

Number of subjects included in analysis

1509

Analysis specification

Pre-specified

Analysis type

superiority ^[9]

P-value

= 0.005294

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.484

Confidence interval

level

95%

sides

2-sided

lower limit

0.287

upper limit

0.815

Notes
[9] - The hazard ratio and its 95% CI were based on Cox Regression Model, stratified by Prostate-specific antigen doubling time (PSADT) (≤ 6 months vs. > 6 months) and use of osteoclast-targeted therapy (No, Yes).

Adverse events

Top of page

Timeframe for reporting adverse events

From start of study drug administration until 30 days after last treatment (last cut-off date 14 JUN 2021)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

24.0

Reporting group title

Darolutamide (DB)

Reporting group description

Subjects received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equivalent to a total daily dose of 1200 mg (double blind [DB]).

Reporting group title

Placebo+Darolutamide (CO)

Reporting group description

Subjects received matching placebo 2 tablets twice daily with food. Subjects from the placebo arm crossed over to receive open-label darolutamide treatment (placebo-darolutamide cross-over [CO]).

Reporting group title

Placebo (DB)

Reporting group description

Subjects received matching placebo 2 tablets twice daily with food (double blind [DB]).

Reporting group title

Darolutamide (DB+OL)

Reporting group description

Subjects received darolutamide 600 mg (2 tablets of 300 mg) twice daily with food, equal to a total daily dose of 1200 mg. Subjects in the darolutamide treatment arm were ongoing with open-label darolutamide treatment (darolutamide double-blind [DB] + open-label [OL]).

Serious adverse events	Darolutamide (DB)	Placebo+Darolutamide (CO)	Placebo (DB)	Darolutamide (DB+OL)
Total subjects affected by serious adverse events
subjects affected / exposed	251 / 954 (26.31%)	43 / 170 (25.29%)	121 / 554 (21.84%)	367 / 954 (38.47%)
number of deaths (all causes)	155	16	137	224
number of deaths resulting from adverse events	38	6	19	63
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Benign hepatic neoplasm
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder cancer
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder neoplasm
subjects affected / exposed	3 / 954 (0.31%)	1 / 170 (0.59%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder transitional cell carcinoma
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Carcinoid tumour
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Choroid melanoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diffuse large B-cell lymphoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric cancer
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	2 / 554 (0.36%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal cancer
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lipoma
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung adenocarcinoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma in situ
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningioma
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mesothelioma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to spine
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neoplasm malignant
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic carcinoma
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Pituitary tumour
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thymoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transitional cell carcinoma
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour pain
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal stromal tumour
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colorectal adenocarcinoma
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma pancreas
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine carcinoma
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
Brain neoplasm
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon neoplasm
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Salivary gland neoplasm
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal neoplasm
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatocellular carcinoma
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neuroendocrine tumour of the lung
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Aortic aneurysm
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic dissection
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Aortic stenosis
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic thrombosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Circulatory collapse
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Hypertension
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoedema
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orthostatic hypotension
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subclavian vein thrombosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iliac artery stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Angioplasty
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder catheterisation
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hip arthroplasty
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia repair
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Orchidectomy
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transurethral prostatectomy
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephrostomy
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary angioplasty
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Artificial urinary sphincter implant
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radiotherapy to brain
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatectomy
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary resection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	4 / 954 (0.42%)	0 / 170 (0.00%)	1 / 554 (0.18%)	6 / 954 (0.63%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 6
Gait disturbance
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sudden death
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Sudden cardiac death
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
General physical health deterioration
subjects affected / exposed	5 / 954 (0.52%)	0 / 170 (0.00%)	0 / 554 (0.00%)	7 / 954 (0.73%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 0	0 / 11
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 4
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatic obstruction
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate induration
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perineal pain
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	3 / 554 (0.54%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	3 / 554 (0.54%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	4 / 954 (0.42%)	0 / 170 (0.00%)	2 / 554 (0.36%)	5 / 954 (0.52%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Epistaxis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary artery thrombosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	5 / 954 (0.52%)	1 / 170 (0.59%)	1 / 554 (0.18%)	7 / 954 (0.73%)
occurrences causally related to treatment / all	1 / 5	0 / 1	1 / 1	1 / 7
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
Pulmonary thrombosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Delirium
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Major depression
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Biopsy prostate
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Body temperature increased
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatic specific antigen increased
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urine output decreased
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angiocardiogram
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	2 / 554 (0.36%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Alcohol poisoning
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Ankle fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bite
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral neck fracture
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Hip fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Patella fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radiation proctitis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Radius fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Subdural haematoma
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stenosis of vesicourethral anastomosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative ileus
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular procedure complication
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Heart injury
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Skull fracture
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft complication
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Flatback syndrome
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated parastomal hernia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Pyloric stenosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	5 / 954 (0.52%)	0 / 170 (0.00%)	0 / 554 (0.00%)	6 / 954 (0.63%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
Angina pectoris
subjects affected / exposed	4 / 954 (0.42%)	1 / 170 (0.59%)	2 / 554 (0.36%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Angina unstable
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arrhythmia
subjects affected / exposed	2 / 954 (0.21%)	1 / 170 (0.59%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis coronary artery
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	8 / 954 (0.84%)	3 / 170 (1.76%)	3 / 554 (0.54%)	9 / 954 (0.94%)
occurrences causally related to treatment / all	0 / 11	0 / 3	0 / 3	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block second degree
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac arrest
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	3 / 554 (0.54%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 2
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 2
Cardiac failure
subjects affected / exposed	8 / 954 (0.84%)	2 / 170 (1.18%)	4 / 554 (0.72%)	12 / 954 (1.26%)
occurrences causally related to treatment / all	0 / 9	0 / 2	0 / 5	0 / 14
deaths causally related to treatment / all	0 / 4	0 / 1	0 / 3	0 / 7
Cardiac failure acute
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Cardiac failure congestive
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Conduction disorder
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery disease
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Coronary artery occlusion
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive heart disease
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Myocardial infarction
subjects affected / exposed	4 / 954 (0.42%)	2 / 170 (1.18%)	2 / 554 (0.36%)	11 / 954 (1.15%)
occurrences causally related to treatment / all	0 / 4	0 / 2	2 / 3	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 1	1 / 1	0 / 3
Myocardial ischaemia
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Palpitations
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus bradycardia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute coronary syndrome
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorder
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Aortic valve disease
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiovascular insufficiency
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Autonomic nervous system imbalance
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bulbar palsy
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Carotid artery stenosis
subjects affected / exposed	2 / 954 (0.21%)	1 / 170 (0.59%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral infarction
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Cerebrovascular accident
subjects affected / exposed	2 / 954 (0.21%)	1 / 170 (0.59%)	3 / 554 (0.54%)	6 / 954 (0.63%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Dizziness
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
Haemorrhagic stroke
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Normal pressure hydrocephalus
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subarachnoid haemorrhage
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	2 / 554 (0.36%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain oedema
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Perineurial cyst
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
IIIrd nerve disorder
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cognitive disorder
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	5 / 954 (0.52%)	1 / 170 (0.59%)	2 / 554 (0.36%)	5 / 954 (0.52%)
occurrences causally related to treatment / all	1 / 6	0 / 1	0 / 2	1 / 6
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
Partial seizures
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Parkinson's disease
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertebrobasilar stroke
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 954 (0.31%)	1 / 170 (0.59%)	0 / 554 (0.00%)	8 / 954 (0.84%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukopenia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphopenia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Autoimmune haemolytic anaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Immune thrombocytopenia
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device dislocation
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device occlusion
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Cataract
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Glaucoma
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal vascular disorder
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Visual impairment
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Macular hole
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal mass
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
Enterocolitis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Gastrointestinal necrosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal pain
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated inguinal hernia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal infarction
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Intestinal ischaemia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Intestinal obstruction
subjects affected / exposed	4 / 954 (0.42%)	0 / 170 (0.00%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatic cyst
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Plicated tongue
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Proctitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	2 / 554 (0.36%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal perforation
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	1 / 1
Umbilical hernia
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumoperitoneum
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal haemorrhage
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower gastrointestinal haemorrhage
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine polyp
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestinal obstruction
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterovesical fistula
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bowel movement irregularity
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hiatus hernia, obstructive
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Obstructive pancreatitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis acute
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic function abnormal
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Liver disorder
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Bile duct stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Biliary obstruction
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermatitis allergic
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin mass
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Azotaemia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Calculus bladder
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysuria
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	3 / 554 (0.54%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	11 / 954 (1.15%)	0 / 170 (0.00%)	7 / 554 (1.26%)	25 / 954 (2.62%)
occurrences causally related to treatment / all	0 / 13	0 / 0	0 / 7	0 / 29
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	3 / 954 (0.31%)	2 / 170 (1.18%)	4 / 554 (0.72%)	8 / 954 (0.84%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 4	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephritis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oliguria
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pollakiuria
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal colic
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	4 / 554 (0.72%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Ureteric obstruction
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ureteric stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	16 / 954 (1.68%)	6 / 170 (3.53%)	20 / 554 (3.61%)	33 / 954 (3.46%)
occurrences causally related to treatment / all	1 / 17	0 / 6	1 / 20	1 / 37
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract disorder
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urine flow decreased
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	7 / 954 (0.73%)	1 / 170 (0.59%)	3 / 554 (0.54%)	11 / 954 (1.15%)
occurrences causally related to treatment / all	0 / 9	0 / 1	0 / 3	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal impairment
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	2 / 554 (0.36%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute kidney injury
subjects affected / exposed	4 / 954 (0.42%)	1 / 170 (0.59%)	3 / 554 (0.54%)	7 / 954 (0.73%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower urinary tract symptoms
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder outlet obstruction
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ureterolithiasis
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	1 / 554 (0.18%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Kyphosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteoarthritis
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	1 / 554 (0.18%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rheumatoid arthritis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rapidly progressive osteoarthritis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal stenosis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis gangrenous
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
Dengue fever
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Endocarditis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Erysipelas
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatitis C
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	2 / 554 (0.36%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infectious mononucleosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Meningitis bacterial
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Osteomyelitis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Perinephric abscess
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	15 / 954 (1.57%)	1 / 170 (0.59%)	6 / 554 (1.08%)	20 / 954 (2.10%)
occurrences causally related to treatment / all	0 / 18	0 / 2	0 / 6	0 / 24
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
Pneumonia pneumococcal
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia staphylococcal
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	0 / 554 (0.00%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sialoadenitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Tick-borne viral encephalitis
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	7 / 954 (0.73%)	1 / 170 (0.59%)	0 / 554 (0.00%)	12 / 954 (1.26%)
occurrences causally related to treatment / all	0 / 7	0 / 1	0 / 0	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vestibular neuronitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	1 / 954 (0.10%)	1 / 170 (0.59%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	2 / 954 (0.21%)	1 / 170 (0.59%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute endocarditis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection bacterial
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infective exacerbation of chronic obstructive airways disease
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal sepsis
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
Wound abscess
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella bacteraemia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral discitis
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal abscess
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial infection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis infective
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	1 / 554 (0.18%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Severe acute respiratory syndrome
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis infective
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Medical device site infection
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	0 / 954 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicella zoster virus infection
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Medical device site joint infection
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 954 (0.00%)	1 / 170 (0.59%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 3
Diverticulitis intestinal perforated
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
Suspected COVID-19
subjects affected / exposed	0 / 954 (0.00%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
Dehydration
subjects affected / exposed	2 / 954 (0.21%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	2 / 954 (0.21%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	3 / 954 (0.31%)	0 / 170 (0.00%)	1 / 554 (0.18%)	3 / 954 (0.31%)
occurrences causally related to treatment / all	0 / 4	0 / 0	1 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	1 / 954 (0.10%)	0 / 170 (0.00%)	0 / 554 (0.00%)	1 / 954 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	4 / 954 (0.42%)	0 / 170 (0.00%)	0 / 554 (0.00%)	4 / 954 (0.42%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0