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Clinical Trial Results:
A Phase III, multicentre, international, randomised, parallel group, double blind cardiovascular safety study of BI 10773 (10 mg and 25 mg administered orally once daily) compared to usual care in type 2 diabetes mellitus (T2DM) patients with increased cardiovascular risk

Summary
EudraCT number	2009-016178-33
Trial protocol	NL DK ES BE FR IT HU PT GB AT GR PL EE CZ
Global end of trial date	13 Apr 2015

Results information
Results version number	v1(current)
This version publication date	29 Apr 2016
First version publication date	29 Apr 2016
Other versions

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

1245.25

ISRCTN number

-

US NCT number

NCT01131676

WHO universal trial number (UTN)

-

Sponsor organisation name

Boehringer Ingelheim

Sponsor organisation address

Binger Strasse 173, Ingelheim am Rhein, Germany, 55216

Public contact

QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 800 2430127, clintriage.rdg@boehringer-ingelheim.com

Scientific contact

QRPE Processes and Systems Coordination, Clinical Trial Information Disclosure, Boehringer Ingelheim, +1 800 2430127, clintriage.rdg@boehringer-ingelheim.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

13 Aug 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Apr 2015

Global end of trial reached?

Yes

Global end of trial date

13 Apr 2015

Was the trial ended prematurely?

No

Main objective of the trial

The primary objective of this event driven study is to determine non inferiority (non inferiority margin of 1.3) of the treatment with two pooled doses (10mg q.d and 25 mg q.d.) of BI 10773 versus placebo on the composite of 3 Major Adverse Cardiovascular Events (MACE): cardiovascular death, non fatal stroke and nonfatal myocardial infarction in patients with type 2 diabetes mellitus and increased cardiovascular risk.

Protection of trial subjects

Monitoring of all patients was performed in accordance with protocol. All subjects were free to withdraw at any time for any reason given.

Background therapy

Standard care therapy for type 2 diabetes and cardiovascular disease .

Evidence for comparator

-

Actual start date of recruitment

26 Aug 2010

Long term follow-up planned

No

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 41

Country: Number of subjects enrolled

Canada: 246

Country: Number of subjects enrolled

New Zealand: 25

Country: Number of subjects enrolled

United States: 2352

Country: Number of subjects enrolled

Hong Kong: 63

Country: Number of subjects enrolled

India: 280

Country: Number of subjects enrolled

Indonesia: 71

Country: Number of subjects enrolled

Japan: 103

Country: Number of subjects enrolled

Korea, Democratic People's Republic of: 494

Country: Number of subjects enrolled

Malaysia: 322

Country: Number of subjects enrolled

Philippines: 366

Country: Number of subjects enrolled

Singapore: 34

Country: Number of subjects enrolled

Sri Lanka: 113

Country: Number of subjects enrolled

Taiwan: 223

Country: Number of subjects enrolled

Thailand: 124

Country: Number of subjects enrolled

Argentina: 395

Country: Number of subjects enrolled

Brazil: 909

Country: Number of subjects enrolled

Colombia: 163

Country: Number of subjects enrolled

Mexico: 140

Country: Number of subjects enrolled

Peru: 244

Country: Number of subjects enrolled

South Africa: 563

Country: Number of subjects enrolled

Austria: 216

Country: Number of subjects enrolled

Belgium: 222

Country: Number of subjects enrolled

Croatia: 220

Country: Number of subjects enrolled

Czech Republic: 26

Country: Number of subjects enrolled

Denmark: 144

Country: Number of subjects enrolled

Estonia: 52

Country: Number of subjects enrolled

France: 144

Country: Number of subjects enrolled

Georgia: 196

Country: Number of subjects enrolled

Greece: 135

Country: Number of subjects enrolled

Hungary: 318

Country: Number of subjects enrolled

Israel: 172

Country: Number of subjects enrolled

Italy: 258

Country: Number of subjects enrolled

Netherlands: 171

Country: Number of subjects enrolled

Norway: 131

Country: Number of subjects enrolled

Poland: 312

Country: Number of subjects enrolled

Portugal: 272

Country: Number of subjects enrolled

Romania: 203

Country: Number of subjects enrolled

Russian Federation: 437

Country: Number of subjects enrolled

Spain: 298

Country: Number of subjects enrolled

Ukraine: 190

Country: Number of subjects enrolled

United Kingdom: 143

Worldwide total number of subjects

11531

EEA total number of subjects

3265

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)

6419

From 65 to 84 years

5060

85 years and over

52

Subject disposition

Top of page

Recruitment details

Patients randomised to treatments Placebo, Empagliflizin 10 mg, Empagliflozin 25 mg in a 1:1:1 ratio. Age for one subject was missing, since EudraCT does not support missing category, the same subject is considered under 18-64 age-group.

Screening details

All subjects were screened for eligibility considering the protocol defined inclusion/exclusion criteria to participate in the trial.

Period 1 title

Discontinuation from treatment

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

Randomisation stratified by: BMI at randomisation (<30 or ≥30 kg/m2), HbA1c at screening (<8.5% or ≥8.5%); geographical region (North America including Australia and New Zealand,Latin America,Europe,Africa,Asia); renal function at screening (normal: eGFR ≥90 mL/min, mild impairment: 60 mL/min ≤ eGFR ≤89 mL/min, moderate impairment: 30 mL/min ≤ eGFR≤59 mL/min).

Are arms mutually exclusive

Yes

Placebo

Arm description

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily). 4 subjects randomised to Placebo were not treated. Although actual number of subjects started is 2337, 2333 were reported to follow the primary analysis set.

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

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily).

Empagliflozin 10 mg

Arm description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 10 mg were not treated. Although actual number of subjects started is 2347, 2345 were reported to follow the primary analysis set.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)

Empagliflozin 25 mg

Arm description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 25 mg were not treated. Although actual number of subjects started is 2344, 2342 were reported to follow the primary analysis set.

Arm type

Experimental

Investigational medicinal product name

Empagliflozin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Number of subjects in period 1 ^[1]	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg
Started	2333	2345	2342
Completed	1650	1790	1800
Not completed	683	555	542
Adverse event, serious fatal	102	89	71
Other than those specified	162	142	125
Non compliant with protocol	15	15	12
Adverse event, non-fatal	201	178	202
Study drug stopped, reason missing	5	3	4
Refusal to continue, not due to AE	172	118	122
Lost to follow-up	15	9	6
Lack of efficacy	11	1	-

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Baseline characteristics are based on patients who were randomised after successfully completing the screening period and received at least one of the trial medication.

Period 2 title

Discontinuation from study (Treated set)

Is this the baseline period?

No

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Are arms mutually exclusive

No

Placebo

Arm description

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily)

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

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily)

Empagliflozin 10 mg

Arm description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)

Arm type

Experimental

Investigational medicinal product name

Empagliflozin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)

Empagliflozin 25 mg

Arm description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Arm type

Experimental

Investigational medicinal product name

Empagliflozin

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Number of subjects in period 2	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg
Started	2333	2345	2342
Final vital status (VS) available	2316	2324	2327
Completed	2266	2264	2279
Not completed	67	81	63
Site closure:Final VS not available (NA)	5	9	7
Consent withdrawn:Final VS not available	8	6	5
Site closure: Final VS available	20	21	19
Lost to FU for 3P-MACE:Final VS NA	4	4	2
Lost to FU for 3PMACE:Final VS available	7	6	5
Consent withdrawn: Final VS available	23	35	25

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily). 4 subjects randomised to Placebo were not treated. Although actual number of subjects started is 2337, 2333 were reported to follow the primary analysis set.

Reporting group title

Empagliflozin 10 mg

Reporting group description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 10 mg were not treated. Although actual number of subjects started is 2347, 2345 were reported to follow the primary analysis set.

Reporting group title

Empagliflozin 25 mg

Reporting group description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 25 mg were not treated. Although actual number of subjects started is 2344, 2342 were reported to follow the primary analysis set.

Reporting group values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	Total
Number of subjects	2333	2345	2342	7020
Age categorical
Units: Subjects
Age Continuous
Treated set (TS): Consists of all randomised patients who received at least 1 dose of study medication. Patients were assigned to treatment groups according to the randomisation scheme.
Units: years
arithmetic mean (standard deviation)	63.2 ( 8.8 )	63 ( 8.6 )	63.2 ( 8.6 )	-
Gender, Male/Female
Units: participants
Female	653	692	659	2004
Male	1680	1653	1683	5016

Subject analysis set title

All Empagliflozin

Subject analysis set type

Full analysis

Subject analysis set description

Patients who received either 10 mg or 25 mg of empagliflozin were pooled into a common empagliflozin treatment group.

Subject analysis sets values	All Empagliflozin
Number of subjects	4687
Age categorical
Units: Subjects
Age Continuous
Treated set (TS): Consists of all randomised patients who received at least 1 dose of study medication. Patients were assigned to treatment groups according to the randomisation scheme.
Units: years
arithmetic mean (standard deviation)	63.1 ( 8.6 )
Gender, Male/Female
Units: participants
Female	1351
Male	3336

End points

Top of page

Reporting group title

Placebo

Reporting group description

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily). 4 subjects randomised to Placebo were not treated. Although actual number of subjects started is 2337, 2333 were reported to follow the primary analysis set.

Reporting group title

Empagliflozin 10 mg

Reporting group description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 10 mg were not treated. Although actual number of subjects started is 2347, 2345 were reported to follow the primary analysis set.

Reporting group title

Empagliflozin 25 mg

Reporting group description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily). 2 subjects randomised to Empagliflozin 25 mg were not treated. Although actual number of subjects started is 2344, 2342 were reported to follow the primary analysis set.

Reporting group title

Placebo

Reporting group description

Oral administration of Placebo matching empagliflozin 10 mg or 25 mg (1 tablet once daily)

Reporting group title

Empagliflozin 10 mg

Reporting group description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)

Reporting group title

Empagliflozin 25 mg

Reporting group description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Subject analysis set title

All Empagliflozin

Subject analysis set type

Full analysis

Subject analysis set description

Patients who received either 10 mg or 25 mg of empagliflozin were pooled into a common empagliflozin treatment group.

Primary: Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point MACE): CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), and non-fatal stroke.

Top of page

End point title

Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point MACE): CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), and non-fatal stroke.

End point description

Time to the first occurrence of any of the following adjudicated components of the primary composite endpoint (3-point major adverse cardiovascular events (MACE)): cardiovascular (CV) death (including fatal stroke and fatal myocardial infarction (MI)), non-fatal MI (excluding silent MI), and non-fatal stroke. Percentage of patients with the event are presented.

End point type

Primary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	2333 ^[1]	2345 ^[2]	2342 ^[3]	4687 ^[4]
Units: percentage of participants
number (not applicable)	12.1	10.4	10.5	10.5

Notes
[1] - TS (evaluable cases)
[2] - TS (evaluable cases)
[3] - TS (evaluable cases)
[4] - TS (evaluable cases)

Statistical analysis 1

Statistical analysis description

Primary objective was to establish the non-inferiority of All empagliflozin relative to placebo for time to first 3-point MACE. A 4-step hierarchical testing strategy was followed for the non-inferiority test of the primary endpoint and then the key secondary endpoint, each at a margin of 1.3, followed by test of superiority of primary and key secondary endpoints.

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

7020

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.0001 ^[6]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.86

Confidence interval

level

95.02%

sides

2-sided

lower limit

0.74

upper limit

0.99

Notes
[5] - The non-inferiority margin was chosen as 1.3 based on Food and Drug Administration (FDA) Guidance for Industry – Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes .
[6] - One-sided test with alpha = 0.0249. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Statistical Analysis 2

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

7020

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0382 ^[7]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.86

Confidence interval

level

95.02%

sides

2-sided

lower limit

0.74

upper limit

0.99

Notes
[7] - Two-sided test with alpha=0.0498. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Secondary: Percentage of participants with composite of all events adjudicated (4-point MACE):CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris

Top of page

End point title

Percentage of participants with composite of all events adjudicated (4-point MACE):CV death (including fatal stroke and fatal MI), non-fatal MI (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris

End point description

The composite of all events adjudicated (4-point MACE): cardiovascular death (including fatal stroke and fatal myocardial infarction), non-fatal myocardial infarction (excluding silent MI), non-fatal stroke and hospitalization for unstable angina pectoris.This is a key secondary endpoint of the trial. Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	2333 ^[8]	2345 ^[9]	2342 ^[10]	4687 ^[11]
Units: percentage of participants
number (not applicable)	14.3	12.8	12.8	12.8

Notes
[8] - TS (evaluable cases)
[9] - TS (evaluable cases)
[10] - TS (evaluable cases)
[11] - TS (evaluable cases)

Statistical analysis 1

Statistical analysis description

A 4-step hierarchical testing strategy was followed for the non-inferiority test of the primary endpoint and then the key secondary endpoint, each at a margin of 1.3, followed by test of superiority of primary and key secondary endpoints.

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

7020

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

< 0.0001 ^[13]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95.02%

sides

2-sided

lower limit

0.78

upper limit

1.01

Notes
[12] - The non-inferiority margin was chosen as 1.3 based on Food and Drug Administration (FDA) Guidance for Industry – Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes
[13] - One-sided test with alpha = 0.0249. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Statistical analysis 2

Statistical analysis description

A 4-step hierarchical testing strategy was followed for the non-inferiority test of the primary endpoint and then the key secondary endpoint, each at a margin of 1.3, followed by test of superiority of primary and key secondary endpoints.

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

7020

Analysis specification

Post-hoc

Analysis type

superiority

P-value

= 0.0795 ^[14]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.89

Confidence interval

level

95.02%

sides

2-sided

lower limit

0.78

upper limit

1.01

Notes
[14] - Two-sided test with alpha=0.0498. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Secondary: Percentage of participants with silent MI

Top of page

End point title

Percentage of participants with silent MI

End point description

Silent MI; defined as presence in the ECG of: - Any Q-wave in leads V2-V3 ≥0.02 seconds or QS complex in leads V2 and V3 - Q-wave ≥0.03 seconds and ≥0.1 mV deep or QS complex in leads I, II, aVL, aVF, or V4-V6 in any two leads of a contiguous lead grouping (I, aVL, V6; V4-V6; II, III, and aVF) - R-wave ≥0.04 seconds in V1-V2 and R/S ≥1 with a concordant positive T-wave in the absence of a conduction defect. It was also required that there had been no adjudicated and confirmed event of either acute MI, hospitalisation for unstable angina, coronary revascularisation procedures or stent thrombosis following randomisation up to and including the date of the specified ECG measurement. Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	1211 ^[15]	1174 ^[16]	1204 ^[17]	2378 ^[18]
Units: percentage of participants
number (not applicable)	1.2	1.6	1.6	1.6

Notes
[15] - TS (evaluable cases)
[16] - TS (evaluable cases)
[17] - TS (evaluable cases)
[18] - TS (evaluable cases)

Statistical analysis 1

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

3589

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.4172 ^[19]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

1.28

Confidence interval

level

95%

sides

2-sided

lower limit

0.7

upper limit

2.33

Notes
[19] - Two-sided test with alpha = 0.05. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo

Secondary: Percentage of participants with heart failure requiring hospitalisation (adjudicated)

Top of page

End point title

Percentage of participants with heart failure requiring hospitalisation (adjudicated)

End point description

Heart failure requiring hospitalisation (adjudicated). Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	2333 ^[20]	2345 ^[21]	2342 ^[22]	4687 ^[23]
Units: percentage of participants
number (not applicable)	4.1	2.6	2.8	2.7

Notes
[20] - TS (evaluable cases)
[21] - TS (evaluable cases)
[22] - TS (evaluable cases)
[23] - TS (evaluable cases)

Statistical analysis 1

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

7020

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.0017 ^[24]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.65

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.85

Notes
[24] - Two-sided test with alpha = 0.05. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Secondary: Percentage of participants with new onset albuminuria

Top of page

End point title

Percentage of participants with new onset albuminuria

End point description

New onset albuminuria defined as urine albumin / creatinine ratio (UACR) ≥30 mg/g. Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	1374 ^[25]	1403 ^[26]	1376 ^[27]	2779 ^[28]
Units: percentage of participants
number (not applicable)	51.2	51.5	51.5	51.5

Notes
[25] - TS (evaluable cases)
[26] - TS (evaluable cases)
[27] - TS (evaluable cases)
[28] - TS (evaluable cases)

Statistical analysis 1

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

4153

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.2547 ^[29]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.95

Confidence interval

level

95%

sides

2-sided

lower limit

0.87

upper limit

1.04

Notes
[29] - Two-sided test with alpha = 0.05. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo

Secondary: Percentage of participants with new onset macroalbuminuria

Top of page

End point title

Percentage of participants with new onset macroalbuminuria

End point description

New onset macroalbuminuria defined as UACR >300 mg/g. Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	2033 ^[30]	2037 ^[31]	2054 ^[32]	4091 ^[33]
Units: percentage of participants
number (not applicable)	16.2	10.9	11.5	11.2

Notes
[30] - TS (evaluable cases)
[31] - TS (evaluable cases)
[32] - TS (evaluable cases)
[33] - TS (evaluable cases)

Statistical analysis 1

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

6124

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[34]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.72

Notes
[34] - Two-sided test with alpha = 0.05. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Secondary: Percentage of participants with composite microvascular outcome

Top of page

End point title

Percentage of participants with composite microvascular outcome

End point description

Composite microvascular outcome defined as: - Initiation of retinal photocoagulation - Vitreous haemorrhage - Diabetes-related blindness, or - New or worsening nephropathy defined as: ◦ New onset of macroalbuminuria; or ◦ Doubling of serum creatinine level accompanied by an eGFR (based on modification of diet in renal disease (MDRD) formula) ≤45 mL/min/1.73m2; or ◦ Initiation of continuous renal replacement therapy, or ◦ Death due to renal disease. Percentage of patients with the event are presented.

End point type

Secondary

End point timeframe

From randomisation to individual end of observation, up to 4.6 years

End point values	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Number of subjects analysed	2068 ^[35]	2057 ^[36]	2075 ^[37]	4132 ^[38]
Units: percentage of participants
number (not applicable)	20.5	13.9	14.1	14

Notes
[35] - TS (evaluable cases)
[36] - TS (evaluable cases)
[37] - TS (evaluable cases)
[38] - TS (evaluable cases)

Statistical analysis 1

Comparison groups

Placebo v All Empagliflozin

Number of subjects included in analysis

6200

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.0001 ^[39]

Method

Cox proportional hazards model

Parameter type

Hazard ratio (HR)

Point estimate

0.62

Confidence interval

level

95%

sides

2-sided

lower limit

0.54

upper limit

0.7

Notes
[39] - Two-sided test with alpha = 0.05. Cox proportional hazards model with factors for treatment, age, gender, categorised BMI, HbA1c, eGFR and geographical region. All Empagliflozin divided by Placebo.

Adverse events

Top of page

Timeframe for reporting adverse events

All AEs, serious and non-serious, occurring during the course of the clinical trial (adverse events up until treatment stop + 7 days); Up to 4.6 years

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

Placebo

Reporting group description

Oral administration of Placebo matching empagliflozin 10 mg and 25 mg (1 tablet once daily)

Reporting group title

Empagliflozin 10 mg

Reporting group description

Oral administration of Empagliflozin 10 mg (BI 10773) film coated tablets (1 tablet once daily)

Reporting group title

Empagliflozin 25 mg

Reporting group description

Oral administration of Empagliflozin 25 mg (BI 10773) film coated tablets (1 tablet once daily)

Reporting group title

All Empagliflozin

Reporting group description

Patients who received either 10 mg or 25 mg of empagliflozin were pooled into a common empagliflozin treatment group for the purposes of the primary analysis.

Serious adverse events	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Total subjects affected by serious adverse events
subjects affected / exposed	988 / 2333 (42.35%)	876 / 2345 (37.36%)	913 / 2342 (38.98%)	1789 / 4687 (38.17%)
number of deaths (all causes)	119	97	79	176
number of deaths resulting from adverse events	2	3	1	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acoustic neuroma
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute lymphocytic leukaemia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Acute myeloid leukaemia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Adenocarcinoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Adenocarcinoma gastric
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Adenocarcinoma of colon
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Adenocarcinoma pancreas
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	3 / 2342 (0.13%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 4
Adenoma benign
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Anogenital warts
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
B-cell lymphoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Basal cell carcinoma
subjects affected / exposed	16 / 2333 (0.69%)	15 / 2345 (0.64%)	12 / 2342 (0.51%)	27 / 4687 (0.58%)
occurrences causally related to treatment / all	0 / 18	0 / 17	0 / 12	0 / 29
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Basosquamous carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Benign hepatic neoplasm
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Benign laryngeal neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Benign lung neoplasm
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Benign neoplasm of adrenal gland
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Benign neoplasm of bladder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Benign neoplasm of prostate
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Benign neoplasm of thyroid gland
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Benign pancreatic neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Benign respiratory tract neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Benign uterine neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Bile duct cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Bladder cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	5 / 2342 (0.21%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 5	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
Bladder cancer recurrent
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bladder transitional cell carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone cancer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bone giant cell tumour benign
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Bowen's disease
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Breast cancer
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cardiac myxoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervix carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cholesteatoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic lymphocytic leukaemia
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clear cell renal cell carcinoma
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon adenoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colon cancer
subjects affected / exposed	2 / 2333 (0.09%)	5 / 2345 (0.21%)	1 / 2342 (0.04%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
Colon cancer metastatic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
Colon neoplasm
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colorectal adenocarcinoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Colorectal cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Endometrial cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Fibroadenoma of breast
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibrosarcoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Follicular thyroid cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastric cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastrointestinal stromal tumour
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Genital neoplasm malignant female
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemangioma of bone
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Haemangioma of liver
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hepatocellular carcinoma
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
Hodgkin's disease stage I
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Invasive ductal breast carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Keratoacanthoma
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large cell lung cancer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Laryngeal cancer
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Laryngeal squamous cell carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Lipoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Lung adenocarcinoma
subjects affected / exposed	2 / 2333 (0.09%)	5 / 2345 (0.21%)	3 / 2342 (0.13%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
Lung cancer metastatic
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Lung carcinoma cell type unspecified stage III
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	7 / 2342 (0.30%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 8	0 / 9
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 4	0 / 4
Lung squamous cell carcinoma stage III
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Lymphocytic lymphoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lymphoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Lymphoproliferative disorder
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Malignant melanoma
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	3 / 2342 (0.13%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malignant melanoma in situ
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Malignant neoplasm of unknown primary site
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Meningioma
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malignant neoplasm progression
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Metastases to bone
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to liver
subjects affected / exposed	3 / 2333 (0.13%)	5 / 2345 (0.21%)	5 / 2342 (0.21%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	1 / 3	0 / 5	0 / 5	0 / 10
deaths causally related to treatment / all	1 / 2	0 / 1	0 / 3	0 / 4
Metastases to lung
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Metastases to lymph nodes
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Metastases to peritoneum
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Metastases to neck
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Metastases to pleura
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastasis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Metastatic malignant melanoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metastatic renal cell carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Neuroendocrine carcinoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Nasopharyngeal cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
Non-Hodgkin's lymphoma stage IV
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Neuroendocrine carcinoma of the skin
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Non-Hodgkin's lymphoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal adenocarcinoma
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
Oesophageal carcinoma
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
POEMS syndrome
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Pancreatic carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	1 / 2	0 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	1 / 2	0 / 1	1 / 3
Papillary serous endometrial carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Papillary thyroid cancer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Parathyroid tumour benign
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pituitary tumour benign
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Penile squamous cell carcinoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Plasma cell myeloma
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	9 / 2333 (0.39%)	11 / 2345 (0.47%)	9 / 2342 (0.38%)	20 / 4687 (0.43%)
occurrences causally related to treatment / all	0 / 9	0 / 11	0 / 9	0 / 20
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Rectal adenocarcinoma
subjects affected / exposed	0 / 2333 (0.00%)	4 / 2345 (0.17%)	3 / 2342 (0.13%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
Prostate cancer recurrent
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Prostatic adenoma
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rectal cancer
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal cancer
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Renal cell carcinoma
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	1 / 1	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal cancer metastatic
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Renal cell carcinoma stage I
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Renal cell carcinoma stage II
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Salivary gland adenoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Skin cancer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Small cell carcinoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sarcoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Splenic marginal zone lymphoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Small cell lung cancer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Squamous cell carcinoma
subjects affected / exposed	3 / 2333 (0.13%)	6 / 2345 (0.26%)	3 / 2342 (0.13%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 3	0 / 7	0 / 3	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of lung
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
Squamous cell carcinoma of skin
subjects affected / exposed	7 / 2333 (0.30%)	4 / 2345 (0.17%)	3 / 2342 (0.13%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 9	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma of the oral cavity
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Thyroid neoplasm
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Tongue neoplasm malignant stage unspecified
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Transitional cell carcinoma
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tumour haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Uterine cancer
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Uterine leiomyoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Vascular disorders
Accelerated hypertension
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Aneurysm
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Angiopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic aneurysm
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	4 / 2342 (0.17%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic arteriosclerosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 dissection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic stenosis
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Arterial disorder
subjects affected / exposed	4 / 2333 (0.17%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arterial haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Arterial occlusive disease
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Arterial stenosis
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerosis
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriovenous fistula
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Arteritis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	5 / 2333 (0.21%)	3 / 2345 (0.13%)	10 / 2342 (0.43%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	0 / 6	0 / 4	0 / 11	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic microangiopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Embolism
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Embolism arterial
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Extremity necrosis
subjects affected / exposed	5 / 2333 (0.21%)	4 / 2345 (0.17%)	8 / 2342 (0.34%)	12 / 4687 (0.26%)
occurrences causally related to treatment / all	0 / 6	0 / 5	0 / 8	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femoral artery embolism
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Femoral artery occlusion
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	5 / 2342 (0.21%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 5	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematoma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	10 / 2333 (0.43%)	4 / 2345 (0.17%)	7 / 2342 (0.30%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 11	0 / 4	0 / 7	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive crisis
subjects affected / exposed	8 / 2333 (0.34%)	3 / 2345 (0.13%)	4 / 2342 (0.17%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 10	0 / 3	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypotension
subjects affected / exposed	9 / 2333 (0.39%)	5 / 2345 (0.21%)	4 / 2342 (0.17%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 9	0 / 5	0 / 4	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive emergency
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemic shock
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Iliac artery occlusion
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Infarction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Intermittent claudication
subjects affected / exposed	2 / 2333 (0.09%)	4 / 2345 (0.17%)	5 / 2342 (0.21%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 5	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemia
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leriche syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Malignant hypertension
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Orthostatic hypotension
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	1 / 3	0 / 1	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral arterial occlusive disease
subjects affected / exposed	23 / 2333 (0.99%)	28 / 2345 (1.19%)	30 / 2342 (1.28%)	58 / 4687 (1.24%)
occurrences causally related to treatment / all	1 / 30	1 / 37	0 / 38	1 / 75
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery aneurysm
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery stenosis
subjects affected / exposed	6 / 2333 (0.26%)	3 / 2345 (0.13%)	9 / 2342 (0.38%)	12 / 4687 (0.26%)
occurrences causally related to treatment / all	0 / 9	0 / 3	0 / 12	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Peripheral coldness
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Peripheral embolism
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral ischaemia
subjects affected / exposed	9 / 2333 (0.39%)	4 / 2345 (0.17%)	11 / 2342 (0.47%)	15 / 4687 (0.32%)
occurrences causally related to treatment / all	0 / 11	0 / 5	0 / 11	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral vascular disorder
subjects affected / exposed	8 / 2333 (0.34%)	3 / 2345 (0.13%)	6 / 2342 (0.26%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	1 / 8	0 / 3	1 / 8	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral venous disease
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subclavian artery stenosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Thrombophlebitis
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombophlebitis superficial
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicose ulceration
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Varicose vein
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular calcification
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Vascular insufficiency
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Venous occlusion
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Venous thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Venous thrombosis limb
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Surgical and medical procedures
Angioplasty
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary angioplasty
subjects affected / exposed	3 / 2333 (0.13%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary arterial stent insertion
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery bypass
subjects affected / exposed	4 / 2333 (0.17%)	3 / 2345 (0.13%)	4 / 2342 (0.17%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 4	0 / 3	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary revascularisation
subjects affected / exposed	5 / 2333 (0.21%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fracture treatment
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Percutaneous coronary intervention
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prophylaxis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stent placement
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cardiac death
subjects affected / exposed	3 / 2333 (0.13%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 3	0 / 4	0 / 2	0 / 6
Asthenia
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chills
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest pain
subjects affected / exposed	28 / 2333 (1.20%)	32 / 2345 (1.36%)	33 / 2342 (1.41%)	65 / 4687 (1.39%)
occurrences causally related to treatment / all	0 / 31	1 / 32	0 / 36	1 / 68
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest discomfort
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Death
subjects affected / exposed	12 / 2333 (0.51%)	10 / 2345 (0.43%)	5 / 2342 (0.21%)	15 / 4687 (0.32%)
occurrences causally related to treatment / all	0 / 12	0 / 10	0 / 5	0 / 15
deaths causally related to treatment / all	0 / 12	0 / 10	0 / 5	0 / 15
Device defective
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device difficult to use
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device deposit issue
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device occlusion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device malfunction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysplasia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Drug ineffective
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Drowning
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Extravasation
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gait disturbance
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Feeling abnormal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised oedema
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Granuloma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hernia
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Impaired healing
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Implant site necrosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Multi-organ failure
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
Malaise
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Oedema peripheral
subjects affected / exposed	5 / 2333 (0.21%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	6 / 2333 (0.26%)	5 / 2345 (0.21%)	15 / 2342 (0.64%)	20 / 4687 (0.43%)
occurrences causally related to treatment / all	0 / 7	0 / 5	1 / 15	1 / 20
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Necrobiosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Oversensing
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pacemaker generated arrhythmia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Perforated ulcer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pain
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral swelling
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Polyp
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Pyrexia
subjects affected / exposed	5 / 2333 (0.21%)	7 / 2345 (0.30%)	2 / 2342 (0.09%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 5	0 / 7	0 / 2	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stent malfunction
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Strangulated hernia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Sudden death
subjects affected / exposed	6 / 2333 (0.26%)	8 / 2345 (0.34%)	5 / 2342 (0.21%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	1 / 6	1 / 8	0 / 5	1 / 13
deaths causally related to treatment / all	1 / 6	1 / 8	0 / 5	1 / 13
Sudden cardiac death
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
Systemic inflammatory response syndrome
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ulcer
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Anaphylactic shock
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Food allergy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Contrast media allergy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Iodine allergy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Social circumstances
Physical assault
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	6 / 2333 (0.26%)	8 / 2345 (0.34%)	10 / 2342 (0.43%)	18 / 4687 (0.38%)
occurrences causally related to treatment / all	0 / 7	0 / 8	1 / 11	1 / 19
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Cystocele
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Endometrial hyperplasia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibrocystic breast disease
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Genital prolapse
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gynaecomastia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Menorrhagia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Ovarian cyst
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Prostatism
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatic obstruction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatitis
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	1 / 2	1 / 2	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Uterine polyp
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Uterine prolapse
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Uterovaginal prolapse
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Vaginal prolapse
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	5 / 2333 (0.21%)	7 / 2345 (0.30%)	1 / 2342 (0.04%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 5	0 / 7	0 / 1	0 / 8
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
Acute respiratory distress syndrome
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	4 / 2333 (0.17%)	5 / 2345 (0.21%)	3 / 2342 (0.13%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 4	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
Allergic sinusitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Asthma
subjects affected / exposed	6 / 2333 (0.26%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 8	0 / 5	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchial secretion retention
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bronchiectasis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bronchitis chronic
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	11 / 2333 (0.47%)	6 / 2345 (0.26%)	10 / 2342 (0.43%)	16 / 4687 (0.34%)
occurrences causally related to treatment / all	0 / 20	0 / 7	0 / 14	0 / 21
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	14 / 2333 (0.60%)	6 / 2345 (0.26%)	9 / 2342 (0.38%)	15 / 4687 (0.32%)
occurrences causally related to treatment / all	0 / 14	0 / 7	0 / 9	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea exertional
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Emphysema
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Epistaxis
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemoptysis
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemothorax
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydrothorax
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Idiopathic pulmonary fibrosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Interstitial lung disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laryngeal oedema
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Lung disorder
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Lung infiltration
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mediastinal haematoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Nasal polyps
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Obstructive airways disorder
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Paranasal cyst
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pleural effusion
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	4 / 2342 (0.17%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 4	0 / 1	1 / 4	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pleural fibrosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Pleurisy
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Pleuritic pain
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pneumothorax
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Pulmonary arterial hypertension
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary congestion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	4 / 2333 (0.17%)	0 / 2345 (0.00%)	6 / 2342 (0.26%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 6	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Pulmonary fibrosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 1	0 / 2
Pulmonary hypertension
subjects affected / exposed	5 / 2333 (0.21%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary mass
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	5 / 2333 (0.21%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 7	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pulmonary thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pulmonary toxicity
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory distress
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Respiratory arrest
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Respiratory failure
subjects affected / exposed	9 / 2333 (0.39%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 9	0 / 2	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
Sinus disorder
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Sleep apnoea syndrome
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Status asthmaticus
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Upper airway obstruction
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Vocal cord polyp
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Vocal cord thickening
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Psychiatric disorders
Anxiety
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Completed suicide
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Confusional state
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	1 / 3	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Delirium
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	5 / 2333 (0.21%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 6	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hallucination
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Insomnia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Major depression
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Mental status changes
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rapid eye movements sleep abnormal
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Substance abuse
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Suicidal ideation
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Suicide attempt
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Hepatobiliary disorders
Bile duct obstruction
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bile duct stone
subjects affected / exposed	0 / 2333 (0.00%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 4	1 / 2	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis
subjects affected / exposed	4 / 2333 (0.17%)	4 / 2345 (0.17%)	5 / 2342 (0.21%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 5	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	4 / 2333 (0.17%)	7 / 2345 (0.30%)	6 / 2342 (0.26%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	0 / 4	0 / 7	0 / 6	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholelithiasis
subjects affected / exposed	7 / 2333 (0.30%)	9 / 2345 (0.38%)	12 / 2342 (0.51%)	21 / 4687 (0.45%)
occurrences causally related to treatment / all	0 / 7	0 / 9	1 / 12	1 / 21
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis chronic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gallbladder disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cholestasis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Hepatic cirrhosis
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	1 / 2	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic steatosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ischaemic hepatitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic function abnormal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Non-alcoholic steatohepatitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Jaundice cholestatic
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Portal hypertension
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Post cholecystectomy syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sphincter of Oddi dysfunction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Angiogram normal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angiogram
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Arteriogram coronary
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anticoagulation drug level above therapeutic
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Blood calcium decreased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Biopsy lung
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Blood creatine phosphokinase MB increased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood glucose fluctuation
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	1 / 2	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood lactate dehydrogenase increased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Blood magnesium decreased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood potassium increased
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood pressure increased
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood urea increased
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Blood pressure orthostatic decreased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cardiac murmur
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
C-reactive protein increased
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac stress test abnormal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Catheterisation cardiac
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ejection fraction decreased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Haemoglobin decreased
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic enzyme increased
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Heart rate irregular
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lipase increased
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Liver function test abnormal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Oxygen consumption increased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Physical examination
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Prostatic specific antigen increased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Scan myocardial perfusion abnormal
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Smear cervix abnormal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Troponin I increased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Weight decreased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 2	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
White blood cell count increased
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Injury, poisoning and procedural complications
Accident at work
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acetabulum fracture
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Anaemia postoperative
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Animal bite
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ankle fracture
subjects affected / exposed	2 / 2333 (0.09%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	1 / 4	0 / 2	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Avulsion fracture
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Back injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chest injury
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Chemical poisoning
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
Cardiac procedure complication
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Clavicle fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Concussion
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery restenosis
subjects affected / exposed	4 / 2333 (0.17%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Contusion
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Deep vein thrombosis postoperative
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Femoral neck fracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fall
subjects affected / exposed	16 / 2333 (0.69%)	9 / 2345 (0.38%)	16 / 2342 (0.68%)	25 / 4687 (0.53%)
occurrences causally related to treatment / all	0 / 16	1 / 9	0 / 16	1 / 25
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Facial bones fracture
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fibula fracture
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	3 / 2333 (0.13%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fracture displacement
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Graft thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Gastrointestinal anastomotic complication
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Head injury
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Hand fracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gun shot wound
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hip fracture
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	7 / 2342 (0.30%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 7	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intentional overdose
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intestinal anastomosis complication
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Joint injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Kidney rupture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Laceration
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Ligament rupture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ligament sprain
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Limb injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Lower limb fracture
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meniscus injury
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple fractures
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Multiple injuries
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Muscle injury
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Open fracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Overdose
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Pelvic fracture
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Periorbital contusion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Peripheral artery restenosis
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periprosthetic fracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Perirenal haematoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Post laminectomy syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Post procedural discomfort
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Post procedural haematuria
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative ileus
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pubis fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Radius fracture
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rib fracture
subjects affected / exposed	6 / 2333 (0.26%)	4 / 2345 (0.17%)	4 / 2342 (0.17%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 6	0 / 4	0 / 4	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Road traffic accident
subjects affected / exposed	6 / 2333 (0.26%)	6 / 2345 (0.26%)	9 / 2342 (0.38%)	15 / 4687 (0.32%)
occurrences causally related to treatment / all	0 / 6	0 / 6	0 / 9	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
Scar
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Seroma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Skin abrasion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Spinal column injury
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Spinal fracture
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Spinal compression fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stab wound
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Splenic rupture
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Subdural haematoma
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural haemorrhage
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tendon injury
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Tendon rupture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Thoracic vertebral fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tongue injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	7 / 2333 (0.30%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Toxicity to various agents
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic haematoma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic intracranial haemorrhage
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Traumatic renal injury
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Traumatic liver injury
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ulna fracture
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Upper limb fracture
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft occlusion
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 3	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Wound
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound dehiscence
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Vascular pseudoaneurysm
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wrist fracture
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Congenital, familial and genetic disorders
Atrial septal defect
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hydrocele
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congenital anomalies of ear ossicles
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Phimosis
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyloric stenosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	10 / 2333 (0.43%)	10 / 2345 (0.43%)	14 / 2342 (0.60%)	24 / 4687 (0.51%)
occurrences causally related to treatment / all	0 / 10	0 / 10	0 / 14	0 / 24
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
Acute myocardial infarction
subjects affected / exposed	42 / 2333 (1.80%)	32 / 2345 (1.36%)	48 / 2342 (2.05%)	80 / 4687 (1.71%)
occurrences causally related to treatment / all	2 / 46	2 / 33	2 / 56	4 / 89
deaths causally related to treatment / all	0 / 7	0 / 3	0 / 6	0 / 9
Angina pectoris
subjects affected / exposed	32 / 2333 (1.37%)	36 / 2345 (1.54%)	42 / 2342 (1.79%)	78 / 4687 (1.66%)
occurrences causally related to treatment / all	2 / 33	2 / 40	3 / 45	5 / 85
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Angina unstable
subjects affected / exposed	87 / 2333 (3.73%)	82 / 2345 (3.50%)	73 / 2342 (3.12%)	155 / 4687 (3.31%)
occurrences causally related to treatment / all	3 / 106	13 / 101	3 / 89	16 / 190
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Aortic valve stenosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Arrhythmia
subjects affected / exposed	2 / 2333 (0.09%)	5 / 2345 (0.21%)	1 / 2342 (0.04%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 5	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Arteriosclerosis coronary artery
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	6 / 2342 (0.26%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 6	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial fibrillation
subjects affected / exposed	14 / 2333 (0.60%)	25 / 2345 (1.07%)	12 / 2342 (0.51%)	37 / 4687 (0.79%)
occurrences causally related to treatment / all	0 / 14	1 / 27	0 / 13	1 / 40
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial flutter
subjects affected / exposed	5 / 2333 (0.21%)	7 / 2345 (0.30%)	4 / 2342 (0.17%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 5	0 / 7	0 / 4	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrial tachycardia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Atrial thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Atrioventricular block
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block complete
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atrioventricular block first degree
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradyarrhythmia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Atrioventricular block second degree
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bradycardia
subjects affected / exposed	11 / 2333 (0.47%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	1 / 11	1 / 2	0 / 4	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bundle branch block bilateral
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bundle branch block right
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cardiac arrest
subjects affected / exposed	12 / 2333 (0.51%)	6 / 2345 (0.26%)	5 / 2342 (0.21%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 12	0 / 6	0 / 5	0 / 11
deaths causally related to treatment / all	0 / 10	0 / 2	0 / 2	0 / 4
Cardiac disorder
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cardiac asthma
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Cardiac failure
subjects affected / exposed	55 / 2333 (2.36%)	42 / 2345 (1.79%)	24 / 2342 (1.02%)	66 / 4687 (1.41%)
occurrences causally related to treatment / all	1 / 67	3 / 50	1 / 25	4 / 75
deaths causally related to treatment / all	0 / 5	0 / 3	0 / 1	0 / 4
Cardiac failure acute
subjects affected / exposed	9 / 2333 (0.39%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 10	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1
Cardiac failure chronic
subjects affected / exposed	0 / 2333 (0.00%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac failure congestive
subjects affected / exposed	45 / 2333 (1.93%)	30 / 2345 (1.28%)	35 / 2342 (1.49%)	65 / 4687 (1.39%)
occurrences causally related to treatment / all	0 / 63	2 / 39	1 / 48	3 / 87
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
Cardiac failure high output
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cardio-respiratory arrest
subjects affected / exposed	6 / 2333 (0.26%)	5 / 2345 (0.21%)	2 / 2342 (0.09%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 6	0 / 5	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 4	0 / 4	0 / 2	0 / 6
Cardiogenic shock
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
Cardiomyopathy
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Cardiopulmonary failure
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
Cardiorenal syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cardiovascular insufficiency
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cardiovascular disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Congestive cardiomyopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Coronary artery disease
subjects affected / exposed	46 / 2333 (1.97%)	21 / 2345 (0.90%)	29 / 2342 (1.24%)	50 / 4687 (1.07%)
occurrences causally related to treatment / all	0 / 48	0 / 26	1 / 33	1 / 59
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
Coronary artery insufficiency
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Coronary artery occlusion
subjects affected / exposed	6 / 2333 (0.26%)	3 / 2345 (0.13%)	7 / 2342 (0.30%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 7	0 / 3	0 / 7	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	5 / 2333 (0.21%)	5 / 2345 (0.21%)	5 / 2342 (0.21%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 6	1 / 5	0 / 6	1 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cyanosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diastolic dysfunction
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive cardiomyopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Hypertensive heart disease
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Intracardiac thrombus
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ischaemic cardiomyopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	4 / 2342 (0.17%)	4 / 4687 (0.09%)
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 / 0
Left atrial dilatation
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Left ventricular dysfunction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Left ventricular failure
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Microvascular coronary artery disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Mitral valve incompetence
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial ischaemia
subjects affected / exposed	15 / 2333 (0.64%)	5 / 2345 (0.21%)	7 / 2342 (0.30%)	12 / 4687 (0.26%)
occurrences causally related to treatment / all	0 / 16	1 / 5	0 / 7	1 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myocardial infarction
subjects affected / exposed	47 / 2333 (2.01%)	50 / 2345 (2.13%)	44 / 2342 (1.88%)	94 / 4687 (2.01%)
occurrences causally related to treatment / all	3 / 48	8 / 55	1 / 48	9 / 103
deaths causally related to treatment / all	0 / 11	0 / 12	0 / 9	0 / 21
Nodal arrhythmia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Myocarditis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial cyst
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Palpitations
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Papillary muscle disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pericarditis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Right ventricular failure
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Postinfarction angina
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Silent myocardial infarction
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	3 / 2342 (0.13%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 1	2 / 3	1 / 3	3 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus arrhythmia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	4 / 2333 (0.17%)	5 / 2345 (0.21%)	1 / 2342 (0.04%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 1	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus bradycardia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sinus node dysfunction
subjects affected / exposed	6 / 2333 (0.26%)	5 / 2345 (0.21%)	3 / 2342 (0.13%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 6	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	5 / 2333 (0.21%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 5	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Systolic dysfunction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia paroxysmal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Trifascicular block
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular extrasystoles
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Ventricular arrhythmia
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ventricular fibrillation
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Ventricular tachycardia
subjects affected / exposed	8 / 2333 (0.34%)	2 / 2345 (0.09%)	5 / 2342 (0.21%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 9	0 / 2	1 / 5	1 / 7
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Nervous system disorders
Altered state of consciousness
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Aphasia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Amnesia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Balance disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Autonomic neuropathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain oedema
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Brain stem haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Brain stem infarction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain stem ischaemia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Brain stem stroke
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Carotid arteriosclerosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Carotid artery occlusion
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	4 / 2342 (0.17%)	4 / 4687 (0.09%)
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 / 0
Carotid artery disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Carotid artery stenosis
subjects affected / exposed	10 / 2333 (0.43%)	7 / 2345 (0.30%)	12 / 2342 (0.51%)	19 / 4687 (0.41%)
occurrences causally related to treatment / all	0 / 10	0 / 7	0 / 12	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Carotid artery thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Carpal tunnel syndrome
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Central nervous system inflammation
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cerebellar infarction
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral arteriosclerosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral artery occlusion
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral artery stenosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cerebral ataxia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cerebral infarction
subjects affected / exposed	7 / 2333 (0.30%)	7 / 2345 (0.30%)	11 / 2342 (0.47%)	18 / 4687 (0.38%)
occurrences causally related to treatment / all	0 / 8	0 / 7	1 / 11	1 / 18
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral ischaemia
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	31 / 2333 (1.33%)	46 / 2345 (1.96%)	37 / 2342 (1.58%)	83 / 4687 (1.77%)
occurrences causally related to treatment / all	1 / 34	0 / 47	0 / 39	0 / 86
deaths causally related to treatment / all	0 / 2	0 / 3	0 / 2	0 / 5
Cerebrovascular disorder
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Cerebrovascular insufficiency
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cervical cord compression
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cervical myelopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Cervical radiculopathy
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cognitive disorder
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Complex partial seizures
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coordination abnormal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Dementia Alzheimer's type
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Diabetic neuropathy
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dizziness
subjects affected / exposed	5 / 2333 (0.21%)	8 / 2345 (0.34%)	5 / 2342 (0.21%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	0 / 5	0 / 8	0 / 5	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysarthria
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Embolic cerebral infarction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Embolic stroke
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Encephalopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Guillain-Barre syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhage intracranial
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Haemorrhagic cerebral infarction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhagic stroke
subjects affected / exposed	4 / 2333 (0.17%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiparesis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hemiplegia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hydrocephalus
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hypercapnic coma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkinesia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive encephalopathy
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoaesthesia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypoglycaemic coma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Hypotonia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
IIIrd nerve paralysis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intercostal neuralgia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Ischaemic cerebral infarction
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ischaemic stroke
subjects affected / exposed	22 / 2333 (0.94%)	18 / 2345 (0.77%)	20 / 2342 (0.85%)	38 / 4687 (0.81%)
occurrences causally related to treatment / all	1 / 26	1 / 18	1 / 24	2 / 42
deaths causally related to treatment / all	0 / 1	0 / 3	0 / 1	0 / 4
Lacunar infarction
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Leukoencephalopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Loss of consciousness
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Lumbar radiculopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Metabolic encephalopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Migraine
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mononeuritis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Monoplegia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscle spasticity
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Myelitis transverse
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myelopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Myoclonus
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Nerve root compression
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Neuroleptic malignant syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Neuropathy peripheral
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paraesthesia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Paraplegia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Paraparesis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Parkinson's disease
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Partial seizures
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral motor neuropathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peroneal nerve palsy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Petit mal epilepsy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Piriformis syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Presyncope
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Radiculopathy
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Sciatica
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
subjects affected / exposed	4 / 2333 (0.17%)	7 / 2345 (0.30%)	5 / 2342 (0.21%)	12 / 4687 (0.26%)
occurrences causally related to treatment / all	0 / 4	0 / 9	0 / 7	0 / 16
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sensory disturbance
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Spinal cord compression
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Spinal epidural haematoma
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Subarachnoid haemorrhage
subjects affected / exposed	3 / 2333 (0.13%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Spondylitic myelopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Syncope
subjects affected / exposed	8 / 2333 (0.34%)	9 / 2345 (0.38%)	18 / 2342 (0.77%)	27 / 4687 (0.58%)
occurrences causally related to treatment / all	0 / 8	2 / 9	1 / 19	3 / 28
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subdural hygroma
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thalamic infarction
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Thrombotic cerebral infarction
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Thrombotic stroke
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Transient ischaemic attack
subjects affected / exposed	23 / 2333 (0.99%)	23 / 2345 (0.98%)	30 / 2342 (1.28%)	53 / 4687 (1.13%)
occurrences causally related to treatment / all	1 / 26	0 / 24	0 / 30	0 / 54
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
VIIth nerve paralysis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vascular encephalopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertebral artery dissection
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Vertebral artery stenosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Vertebrobasilar insufficiency
subjects affected / exposed	3 / 2333 (0.13%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vocal cord paresis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	12 / 2333 (0.51%)	8 / 2345 (0.34%)	7 / 2342 (0.30%)	15 / 4687 (0.32%)
occurrences causally related to treatment / all	1 / 12	0 / 8	0 / 7	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Coagulopathy
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Febrile neutropenia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Haemorrhagic anaemia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypereosinophilic syndrome
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypochromic anaemia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypocoagulable state
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Iron deficiency anaemia
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	4 / 2342 (0.17%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 4	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Microcytic anaemia
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Normochromic normocytic anaemia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Thrombocytopenia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ear and labyrinth disorders
Deafness
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cerumen impaction
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Deafness unilateral
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sudden hearing loss
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Tinnitus
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tympanic membrane perforation
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo
subjects affected / exposed	7 / 2333 (0.30%)	2 / 2345 (0.09%)	9 / 2342 (0.38%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 8	0 / 2	0 / 10	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vertigo positional
subjects affected / exposed	6 / 2333 (0.26%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 6	0 / 0	0 / 4	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Amaurosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Blindness
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Blindness unilateral
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cataract
subjects affected / exposed	9 / 2333 (0.39%)	13 / 2345 (0.55%)	11 / 2342 (0.47%)	24 / 4687 (0.51%)
occurrences causally related to treatment / all	0 / 9	0 / 16	0 / 13	0 / 29
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cataract cortical
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Corneal degeneration
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic retinopathy
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Exfoliation syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Glaucoma
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 5	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Keratopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Macular fibrosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Macular oedema
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Papilloedema
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal artery occlusion
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 3	1 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	0 / 2333 (0.00%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 0	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Retinal tear
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Retinoschisis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Retinopathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Visual acuity reduced
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous haemorrhage
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vitreous opacities
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal hernia
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	5 / 2333 (0.21%)	5 / 2345 (0.21%)	2 / 2342 (0.09%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 5	0 / 5	0 / 2	0 / 7
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Abdominal hernia obstructive
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Abdominal pain lower
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Abdominal pain upper
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal fissure
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anal fistula
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bezoar
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Chronic gastritis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Colitis
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Colitis ischaemic
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Colon dysplasia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Constipation
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Crohn's disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Dental caries
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic gastroparesis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Diabetic gastropathy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Diarrhoea
subjects affected / exposed	6 / 2333 (0.26%)	6 / 2345 (0.26%)	4 / 2342 (0.17%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 6	0 / 7	0 / 5	0 / 12
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal perforation
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Diverticulum
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diverticulum intestinal
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Duodenal ulcer
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenal ulcer perforation
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Duodenitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Dysphagia
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dyspepsia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Erosive duodenitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Epigastric discomfort
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Food poisoning
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Faecaloma
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric perforation
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastric polyps
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastric ulcer
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Gastritis
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	7 / 2342 (0.30%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 7	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis erosive
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastric ulcer perforation
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastritis haemorrhagic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroduodenal ulcer
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Gastrointestinal angiodysplasia
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastroduodenitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorder
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gastrointestinal haemorrhage
subjects affected / exposed	9 / 2333 (0.39%)	4 / 2345 (0.17%)	4 / 2342 (0.17%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 10	0 / 4	0 / 5	0 / 9
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	5 / 2333 (0.21%)	7 / 2345 (0.30%)	3 / 2342 (0.13%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 6	0 / 7	0 / 3	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gingival bleeding
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal inflammation
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Haematochezia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoidal haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids thrombosed
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Hiatus hernia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Ileus
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Ileus paralytic
subjects affected / exposed	3 / 2333 (0.13%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Impaired gastric emptying
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Incarcerated umbilical hernia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Inguinal hernia
subjects affected / exposed	3 / 2333 (0.13%)	5 / 2345 (0.21%)	4 / 2342 (0.17%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 3	0 / 5	0 / 4	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia strangulated
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Intestinal haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal ischaemia
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Intestinal obstruction
subjects affected / exposed	5 / 2333 (0.21%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 5	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Irritable bowel syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intestinal perforation
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Large intestinal ulcer
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Large intestine polyp
subjects affected / exposed	0 / 2333 (0.00%)	5 / 2345 (0.21%)	0 / 2342 (0.00%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 0	0 / 5	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Localised intraabdominal fluid collection
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Lumbar hernia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Mallory-Weiss syndrome
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Melaena
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Nausea
subjects affected / exposed	2 / 2333 (0.09%)	4 / 2345 (0.17%)	2 / 2342 (0.09%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Mesenteric vein thrombosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Oesophageal stenosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Oesophagitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pancreatitis
subjects affected / exposed	4 / 2333 (0.17%)	3 / 2345 (0.13%)	3 / 2342 (0.13%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 3	0 / 6	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 3	0 / 1	2 / 3	2 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis chronic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis relapsing
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peptic ulcer
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peptic ulcer haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peptic ulcer perforation
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Peritoneal haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Rectal haemorrhage
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	1 / 2333 (0.04%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Small intestinal perforation
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Stress ulcer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	5 / 2342 (0.21%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 6	0 / 8
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
Umbilical hernia
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis mesenteric vessel
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Varices oesophageal
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Volvulus
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	2 / 2333 (0.09%)	3 / 2345 (0.13%)	4 / 2342 (0.17%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 3	0 / 4	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cold sweat
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Dermal cyst
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dermatitis contact
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic bullosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot
subjects affected / exposed	12 / 2333 (0.51%)	10 / 2345 (0.43%)	11 / 2342 (0.47%)	21 / 4687 (0.45%)
occurrences causally related to treatment / all	0 / 14	0 / 10	0 / 14	0 / 24
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eczema
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Erythema
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Erythrodermic psoriasis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Ingrowing nail
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Leukoplakia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Neuropathic ulcer
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pemphigus
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Skin fibrosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Skin necrosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Skin ulcer
subjects affected / exposed	10 / 2333 (0.43%)	6 / 2345 (0.26%)	11 / 2342 (0.47%)	17 / 4687 (0.36%)
occurrences causally related to treatment / all	0 / 13	0 / 7	0 / 12	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Skin ulcer haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Urticaria
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	32 / 2333 (1.37%)	26 / 2345 (1.11%)	19 / 2342 (0.81%)	45 / 4687 (0.96%)
occurrences causally related to treatment / all	3 / 34	0 / 27	4 / 19	4 / 46
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Acute prerenal failure
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Albuminuria
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bladder neck sclerosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Anuria
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bladder outlet obstruction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Calculus bladder
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Calculus ureteric
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 4	0 / 4	0 / 2	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Calculus urinary
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis glandularis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic kidney disease
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis haemorrhagic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic nephropathy
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dysuria
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	1 / 1	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Haematuria
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypertensive nephropathy
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Lower urinary tract symptoms
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Microalbuminuria
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Nephritis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Nephrolithiasis
subjects affected / exposed	3 / 2333 (0.13%)	3 / 2345 (0.13%)	7 / 2342 (0.30%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 7	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephropathy
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Nephrotic syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Obstructive uropathy
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Oliguria
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Polyuria
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal artery arteriosclerosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal artery stenosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Renal colic
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Renal cyst
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Renal impairment
subjects affected / exposed	2 / 2333 (0.09%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	10 / 2333 (0.43%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 11	0 / 2	1 / 4	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Renal tubular necrosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal infarct
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Stress urinary incontinence
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tubulointerstitial nephritis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Ureteric obstruction
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urethral stenosis
subjects affected / exposed	2 / 2333 (0.09%)	4 / 2345 (0.17%)	0 / 2342 (0.00%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 4	0 / 0	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary bladder haemorrhage
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Urinary bladder polyp
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary incontinence
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary retention
subjects affected / exposed	3 / 2333 (0.13%)	4 / 2345 (0.17%)	5 / 2342 (0.21%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 3	0 / 5	1 / 5	1 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Endocrine disorders
Basedow's disease
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Goitre
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Hyperparathyroidism
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperparathyroidism primary
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Hyperthyroidism
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 2333 (0.17%)	1 / 2345 (0.04%)	5 / 2342 (0.21%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 5	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arthritis
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	9 / 2333 (0.39%)	3 / 2345 (0.13%)	8 / 2342 (0.34%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 9	0 / 3	0 / 8	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bursitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bone fistula
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cervical spinal stenosis
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Costochondritis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Dupuytren's contracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dactylitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Foot deformity
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	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 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Fistula
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Fracture nonunion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Fracture delayed union
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Gouty arthritis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Gouty tophus
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intervertebral disc compression
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Intervertebral disc degeneration
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Intervertebral disc protrusion
subjects affected / exposed	10 / 2333 (0.43%)	4 / 2345 (0.17%)	6 / 2342 (0.26%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 10	0 / 4	0 / 6	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Intervertebral disc disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Lumbar spinal stenosis
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower extremity mass
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Muscle tightness
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscle twitching
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscular weakness
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal chest pain
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Musculoskeletal pain
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal disorder
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myofascial pain syndrome
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Myalgia
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Myositis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Neck pain
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Neuropathic arthropathy
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteitis deformans
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Osteoarthritis
subjects affected / exposed	15 / 2333 (0.64%)	15 / 2345 (0.64%)	17 / 2342 (0.73%)	32 / 4687 (0.68%)
occurrences causally related to treatment / all	0 / 16	0 / 16	0 / 18	0 / 34
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomalacia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteonecrosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Osteoporosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Osteoporotic fracture
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pain in extremity
subjects affected / exposed	4 / 2333 (0.17%)	3 / 2345 (0.13%)	6 / 2342 (0.26%)	9 / 4687 (0.19%)
occurrences causally related to treatment / all	0 / 6	0 / 3	0 / 6	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pathological fracture
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periarthritis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rhabdomyolysis
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	5 / 2342 (0.21%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 2	0 / 1	1 / 5	1 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rotator cuff syndrome
subjects affected / exposed	1 / 2333 (0.04%)	6 / 2345 (0.26%)	1 / 2342 (0.04%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 6	0 / 1	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal column stenosis
subjects affected / exposed	6 / 2333 (0.26%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 6	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal osteoarthritis
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spinal pain
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Spondylitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Spondylolisthesis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Synovitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Tendonitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tenosynovitis stenosans
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Trigger finger
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Infections and infestations
Abdominal abscess
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal wall abscess
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Abscess limb
subjects affected / exposed	3 / 2333 (0.13%)	6 / 2345 (0.26%)	2 / 2342 (0.09%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 3	0 / 6	0 / 2	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Abscess of eyelid
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Acute sinusitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Amoebiasis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Amoebic dysentery
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Anal abscess
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Appendicitis
subjects affected / exposed	3 / 2333 (0.13%)	5 / 2345 (0.21%)	3 / 2342 (0.13%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	0 / 3	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis perforated
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Arteriosclerotic gangrene
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Arthritis bacterial
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bacteraemia
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bacterial sepsis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Biliary tract infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bone abscess
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Bronchitis
subjects affected / exposed	10 / 2333 (0.43%)	5 / 2345 (0.21%)	5 / 2342 (0.21%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 10	0 / 5	0 / 5	0 / 10
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis viral
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Bronchopneumonia
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	3 / 2342 (0.13%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 3	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Catheter site infection
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cellulitis
subjects affected / exposed	20 / 2333 (0.86%)	11 / 2345 (0.47%)	17 / 2342 (0.73%)	28 / 4687 (0.60%)
occurrences causally related to treatment / all	0 / 24	0 / 20	0 / 17	0 / 37
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
Cellulitis gangrenous
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis of male external genital organ
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cellulitis staphylococcal
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Cholecystitis infective
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Chronic sinusitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile colitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Cutaneous larva migrans
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Cystitis bacterial
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic foot infection
subjects affected / exposed	6 / 2333 (0.26%)	5 / 2345 (0.21%)	7 / 2342 (0.30%)	12 / 4687 (0.26%)
occurrences causally related to treatment / all	0 / 8	0 / 6	0 / 8	0 / 14
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Device related sepsis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Diverticulitis
subjects affected / exposed	3 / 2333 (0.13%)	3 / 2345 (0.13%)	0 / 2342 (0.00%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 3	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic gangrene
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Eczema infected
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Ear infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Endocarditis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Empyema
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis infectious
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Enterocolitis viral
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Endophthalmitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Epididymitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	9 / 2333 (0.39%)	8 / 2345 (0.34%)	5 / 2342 (0.21%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	0 / 9	0 / 8	0 / 5	0 / 13
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Escherichia sepsis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Furuncle
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Febrile infection
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	15 / 2333 (0.64%)	18 / 2345 (0.77%)	15 / 2342 (0.64%)	33 / 4687 (0.70%)
occurrences causally related to treatment / all	0 / 16	1 / 18	2 / 17	3 / 35
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gallbladder empyema
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gangrene
subjects affected / exposed	8 / 2333 (0.34%)	10 / 2345 (0.43%)	6 / 2342 (0.26%)	16 / 4687 (0.34%)
occurrences causally related to treatment / all	0 / 8	0 / 13	0 / 6	0 / 19
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Gastroenteritis viral
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Gastrointestinal infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Gastrointestinal protozoal infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Giardiasis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
H1N1 influenza
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infected skin ulcer
subjects affected / exposed	4 / 2333 (0.17%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 4	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Infectious colitis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Incision site infection
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Infectious pleural effusion
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Influenza
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Inguinal hernia gangrenous
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Infusion site infection
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Intestinal fistula infection
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Intestinal tuberculosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Klebsiella infection
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Labyrinthitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Liver abscess
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Lobar pneumonia
subjects affected / exposed	3 / 2333 (0.13%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Localised infection
subjects affected / exposed	5 / 2333 (0.21%)	2 / 2345 (0.09%)	4 / 2342 (0.17%)	6 / 4687 (0.13%)
occurrences causally related to treatment / all	0 / 5	0 / 2	0 / 4	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	4 / 2333 (0.17%)	8 / 2345 (0.34%)	2 / 2342 (0.09%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 5	0 / 9	0 / 2	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection bacterial
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lung infection
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lyme disease
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Mediastinitis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Meningitis bacterial
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Meningitis streptococcal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis tuberculous
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Muscle abscess
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Myelitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Nasal abscess
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Oesophageal candidiasis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Osteomyelitis acute
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Osteomyelitis
subjects affected / exposed	5 / 2333 (0.21%)	5 / 2345 (0.21%)	9 / 2342 (0.38%)	14 / 4687 (0.30%)
occurrences causally related to treatment / all	0 / 5	0 / 6	0 / 9	0 / 15
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis bacterial
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Osteomyelitis chronic
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Otitis externa
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Otitis media
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonitis
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Periodontitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pertussis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pharyngotonsillitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	53 / 2333 (2.27%)	41 / 2345 (1.75%)	38 / 2342 (1.62%)	79 / 4687 (1.69%)
occurrences causally related to treatment / all	0 / 63	0 / 45	0 / 41	0 / 86
deaths causally related to treatment / all	0 / 5	0 / 3	0 / 3	0 / 6
Pneumonia bacterial
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pneumonia fungal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Pneumonia haemophilus
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural infection
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Postoperative wound infection
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural sepsis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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 / 1	0 / 1
Pseudomonal sepsis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Prostatic abscess
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Pulmonary mycosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Psoas abscess
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary tuberculosis
subjects affected / exposed	2 / 2333 (0.09%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	6 / 2333 (0.26%)	4 / 2345 (0.17%)	1 / 2342 (0.04%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	1 / 6	1 / 4	1 / 1	2 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	5 / 2342 (0.21%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 5	1 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	7 / 2333 (0.30%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 7	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
Pyelonephritis chronic
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Salmonellosis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Rhinitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Sepsis
subjects affected / exposed	5 / 2333 (0.21%)	7 / 2345 (0.30%)	6 / 2342 (0.26%)	13 / 4687 (0.28%)
occurrences causally related to treatment / all	0 / 5	0 / 7	1 / 6	1 / 13
deaths causally related to treatment / all	0 / 3	0 / 3	0 / 1	0 / 4
Scrotal abscess
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
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
Septic encephalopathy
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Septic shock
subjects affected / exposed	8 / 2333 (0.34%)	2 / 2345 (0.09%)	5 / 2342 (0.21%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 8	0 / 2	1 / 5	1 / 7
deaths causally related to treatment / all	0 / 4	0 / 2	1 / 1	1 / 3
Sinusitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Skin infection
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Staphylococcal skin infection
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Staphylococcal sepsis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Staphylococcal infection
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Tonsillitis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Tracheobronchitis
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	0 / 2342 (0.00%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Tuberculous pleurisy
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	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	2 / 2333 (0.09%)	1 / 2345 (0.04%)	2 / 2342 (0.09%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 4	0 / 1	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection pseudomonal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Urinary tract infection
subjects affected / exposed	16 / 2333 (0.69%)	13 / 2345 (0.55%)	16 / 2342 (0.68%)	29 / 4687 (0.62%)
occurrences causally related to treatment / all	4 / 16	6 / 14	3 / 16	9 / 30
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection fungal
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	3 / 2342 (0.13%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	3 / 2333 (0.13%)	6 / 2345 (0.26%)	11 / 2342 (0.47%)	17 / 4687 (0.36%)
occurrences causally related to treatment / all	0 / 3	2 / 6	4 / 12	6 / 18
deaths causally related to treatment / all	0 / 0	1 / 1	1 / 1	2 / 2
Vaginal cellulitis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Vestibular neuronitis
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Varicella
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 2333 (0.00%)	2 / 2345 (0.09%)	5 / 2342 (0.21%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 5	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	3 / 2333 (0.13%)	4 / 2345 (0.17%)	3 / 2342 (0.13%)	7 / 4687 (0.15%)
occurrences causally related to treatment / all	0 / 3	0 / 4	0 / 3	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Wound sepsis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	1 / 2342 (0.04%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 1	1 / 1	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	5 / 2333 (0.21%)	5 / 2345 (0.21%)	5 / 2342 (0.21%)	10 / 4687 (0.21%)
occurrences causally related to treatment / all	0 / 5	1 / 5	1 / 6	2 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetes mellitus
subjects affected / exposed	6 / 2333 (0.26%)	3 / 2345 (0.13%)	2 / 2342 (0.09%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	0 / 6	0 / 3	0 / 2	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 1
Diabetes mellitus inadequate control
subjects affected / exposed	6 / 2333 (0.26%)	8 / 2345 (0.34%)	3 / 2342 (0.13%)	11 / 4687 (0.23%)
occurrences causally related to treatment / all	0 / 6	0 / 8	0 / 3	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic complication
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Diabetic ketoacidosis
subjects affected / exposed	0 / 2333 (0.00%)	3 / 2345 (0.13%)	1 / 2342 (0.04%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 0	0 / 3	0 / 1	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Diabetic metabolic decompensation
subjects affected / exposed	1 / 2333 (0.04%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Fluid overload
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Gout
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperglycaemia
subjects affected / exposed	14 / 2333 (0.60%)	5 / 2345 (0.21%)	3 / 2342 (0.13%)	8 / 4687 (0.17%)
occurrences causally related to treatment / all	1 / 15	0 / 5	0 / 3	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	5 / 2333 (0.21%)	2 / 2345 (0.09%)	3 / 2342 (0.13%)	5 / 4687 (0.11%)
occurrences causally related to treatment / all	1 / 5	0 / 2	0 / 3	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypernatraemia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypervolaemia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1
Hypoglycaemia
subjects affected / exposed	17 / 2333 (0.73%)	10 / 2345 (0.43%)	9 / 2342 (0.38%)	19 / 4687 (0.41%)
occurrences causally related to treatment / all	0 / 21	4 / 11	2 / 9	6 / 20
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
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
Hypokalaemia
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 2333 (0.04%)	2 / 2345 (0.09%)	2 / 2342 (0.09%)	4 / 4687 (0.09%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Hypovolaemia
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Insulin resistance
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	0 / 2342 (0.00%)	0 / 4687 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Lactic acidosis
subjects affected / exposed	0 / 2333 (0.00%)	1 / 2345 (0.04%)	0 / 2342 (0.00%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	1 / 2333 (0.04%)	0 / 2345 (0.00%)	2 / 2342 (0.09%)	2 / 4687 (0.04%)
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
Lipomatosis
subjects affected / exposed	0 / 2333 (0.00%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
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
Obesity
subjects affected / exposed	3 / 2333 (0.13%)	2 / 2345 (0.09%)	1 / 2342 (0.04%)	3 / 4687 (0.06%)
occurrences causally related to treatment / all	0 / 3	0 / 2	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	2 / 2333 (0.09%)	0 / 2345 (0.00%)	1 / 2342 (0.04%)	1 / 4687 (0.02%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	Empagliflozin 10 mg	Empagliflozin 25 mg	All Empagliflozin
Total subjects affected by non serious adverse events
subjects affected / exposed	1690 / 2333 (72.44%)	1556 / 2345 (66.35%)	1551 / 2342 (66.23%)	3107 / 4687 (66.29%)
Vascular disorders
Hypertension
subjects affected / exposed	210 / 2333 (9.00%)	154 / 2345 (6.57%)	176 / 2342 (7.51%)	330 / 4687 (7.04%)
occurrences all number	251	176	209	385
Nervous system disorders
Dizziness
subjects affected / exposed	151 / 2333 (6.47%)	170 / 2345 (7.25%)	173 / 2342 (7.39%)	343 / 4687 (7.32%)
occurrences all number	198	215	245	460
Headache
subjects affected / exposed	123 / 2333 (5.27%)	100 / 2345 (4.26%)	124 / 2342 (5.29%)	224 / 4687 (4.78%)
occurrences all number	158	146	166	312
General disorders and administration site conditions
Oedema peripheral
subjects affected / exposed	155 / 2333 (6.64%)	84 / 2345 (3.58%)	75 / 2342 (3.20%)	159 / 4687 (3.39%)
occurrences all number	171	96	83	179
Gastrointestinal disorders
Constipation
subjects affected / exposed	109 / 2333 (4.67%)	91 / 2345 (3.88%)	119 / 2342 (5.08%)	210 / 4687 (4.48%)
occurrences all number	117	99	130	229
Diarrhoea
subjects affected / exposed	171 / 2333 (7.33%)	145 / 2345 (6.18%)	144 / 2342 (6.15%)	289 / 4687 (6.17%)
occurrences all number	217	184	169	353
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	146 / 2333 (6.26%)	119 / 2345 (5.07%)	108 / 2342 (4.61%)	227 / 4687 (4.84%)
occurrences all number	177	133	124	257
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	130 / 2333 (5.57%)	107 / 2345 (4.56%)	148 / 2342 (6.32%)	255 / 4687 (5.44%)
occurrences all number	142	119	169	288
Back pain
subjects affected / exposed	148 / 2333 (6.34%)	149 / 2345 (6.35%)	166 / 2342 (7.09%)	315 / 4687 (6.72%)
occurrences all number	181	168	178	346
Pain in extremity
subjects affected / exposed	133 / 2333 (5.70%)	114 / 2345 (4.86%)	101 / 2342 (4.31%)	215 / 4687 (4.59%)
occurrences all number	147	128	113	241
Infections and infestations
Bronchitis
subjects affected / exposed	164 / 2333 (7.03%)	129 / 2345 (5.50%)	117 / 2342 (5.00%)	246 / 4687 (5.25%)
occurrences all number	223	157	150	307
Influenza
subjects affected / exposed	165 / 2333 (7.07%)	134 / 2345 (5.71%)	149 / 2342 (6.36%)	283 / 4687 (6.04%)
occurrences all number	237	181	191	372
Nasopharyngitis
subjects affected / exposed	217 / 2333 (9.30%)	210 / 2345 (8.96%)	220 / 2342 (9.39%)	430 / 4687 (9.17%)
occurrences all number	301	291	289	580
Upper respiratory tract infection
subjects affected / exposed	199 / 2333 (8.53%)	191 / 2345 (8.14%)	175 / 2342 (7.47%)	366 / 4687 (7.81%)
occurrences all number	266	266	266	532
Urinary tract infection
subjects affected / exposed	344 / 2333 (14.74%)	339 / 2345 (14.46%)	337 / 2342 (14.39%)	676 / 4687 (14.42%)
occurrences all number	538	598	578	1176
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	423 / 2333 (18.13%)	217 / 2345 (9.25%)	202 / 2342 (8.63%)	419 / 4687 (8.94%)
occurrences all number	1188	442	405	847
Hypoglycaemia
subjects affected / exposed	685 / 2333 (29.36%)	694 / 2345 (29.59%)	673 / 2342 (28.74%)	1367 / 4687 (29.17%)
occurrences all number	5225	4199	4246	8445

More information

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Were there any global substantial amendments to the protocol? Yes

22 Sep 2010

With the introduction of this amendment, cardiovascular outcome events were exempt from the expedited unblinded reporting process if they occurred during the randomised treatment period to preclude reporting of unblinded outcome events while this double-blind study was ongoing. Cardiovascular outcome events were to be reported in specific eCRF pages instead of on paper SAE forms since the reporting of outcome events by treatment group during the trial (by anyone except the DMC) could potentially jeopardise the integrity of the trial. Cardiovascular outcome events that occurred during the screening/run in phase were to be considered as SAEs and not as outcome events. Additionally, hepatic injury was added a significant AE to comply with FDA guidelines for DILI.

22 Apr 2011

Inclusion criterion:Maximum HbA1c for treatment naïve patients was raised to 9.0% from 8.0% and definition of patients with high CV risk was expanded to include single vessel disease,and further clarification of criteria to be met for inclusion of patients with peripheral artery disease,unstable angina,multivessel disease was provided. Exclusion criteria:Acute coronary syndrome, stroke or TIA within 2 months prior to informed consent was added; sibutramine and orlistat were removed as specifically named anti-obesity drugs. Duration of follow-up after regular completion of treatment period was increased from 1 to 4 weeks. Endpoints:Primary endpoint wording was clarified to indicate when patients without events would be censored,Weight and waist circumference measurements at Week 12 were added as further endpoints, Heart failure requiring hospitalization moved from tertiary CV endpoints to secondary endpoints; composite microvascular outcome added as secondary endpoint; Hospitalisation for unstable angina and components of microvascular composite endpoint added as tertiary endpoints.With regard to hypoglycaemic events to be documented in the eCRF,every episode of plasma glucose below 70 was corrected to ≤70 mg/dL (3.9 mmol/L). Clarification of safety laboratory assessments procedures. Statistical analyses:Age & gender were added as covariates to primary analysis model; clarification of non-inferiority margin and order of testing for primary, secondary endpoints both for non-inferiority and then superiority;a 4-step hierarchical testing strategy to include key secondary endpoint was specified. Trial design description was clarified to indicate that randomisation would be stopped after 4000 patients had been randomised. Clarified that while there was no interim analysis planned on the trial level, there was a pre-specified meta-analysis to assess the cardiovascular safety profile of empagliflozin, which included data from this trial.

29 Dec 2011

The non-inferiority margin of 1.8 and the 2 corresponding tests (of the primary and key secondary endpoint), defined as steps 1 and 2 in the hierarchical testing strategy were removed. Hence the test for non-inferiority of the primary endpoint using the non-inferiority margin of 1.3 was defined to be the first test, followed by testing non inferiority of key secondary endpoint etc. Number of patients with primary endpoint events required was changed from 137 to 691 to ensure a power of 90% for testing non-inferiority based on margin of 1.3, using an overall one-sided alpha of 0.025 and 0.0249 for the final analysis. Total number of planned randomised patients was increased from 4000 to 7000 . Planned treatment duration of the patients was changed from an anticipated 206 weeks to approximately 300 to 420 weeks. An interim analysis of this trial to support a New Drug Application (NDA) was part of the cardiovascular meta-analysis using the interim data of this trial. It was projected that approximately 80 confirmed primary events would have been observed from this trial at that time. The interim analysis and the cardiovascular meta-analysis were to be performed by a team independent from the 1245.25 trial team so that the trial team remained blinded to the results. A Haybittle-Peto boundary was used to maintain the experiment-wise overall α level of 0.025. Clarification, that primary & key secondary endpoints did not include silent MI. Further secondary endpoints were revised to new onset albuminuria defined as UACR ≥30 mg/g and new onset macroalbuminuria ≥300 mg/g. Death due to renal disease was added to definition of new or worsening nephropathy. Weight & waist circumference were to be measured annually. hs CR, hs Troponin T, cystatin C, indicators of cardiac risk were to be measured. Procedures for clinical evaluation of liver injury were added. An additional sample for assessment of PK in AESIs was to be collected.

15 Oct 2013

Main changes: - Clarification that the follow-up period of 4 weeks means 30 days - Procedures to be performed for patients on study medication at the time of study completion were clarified - It was clarified that a minimum of 691 events for the planned primary analysis referred to 3-point MACE - The central adjudication of malignancies and hepatic events was added

Were there any global interruptions to the trial? No

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

2 sets of duplicates (4 patients (pts) ) were counted only once. 652 sites were initiated and 611 enrolled. One site transferred all pts to other sites. 27 pts randomised and 13 pts screened were excluded from analyses due to serious non-compliance

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