Trial Outcomes & Findings for A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events (NCT NCT01959529)

NCT ID: NCT01959529

Last Updated: 2019-07-24

Results Overview

Time from randomisation to first occurrence of an event adjudication committee (EAC)-confirmed 3-component major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction, or nonfatal stroke. Events with EAC-confirmed onset date between randomisation and individual end of trial were included in the analyses. The number of subjects experiencing first EAC-confirmed MACEs, date between randomisation to the end of trial, both days included were presented. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 7637 participants
• Primary outcome timeframe: From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)
• Results posted on: 2019-07-24

Participant Flow

The trial was conducted at 438 sites in 20 countries as follows: Algeria: 6; Argentina: 4; Brazil: 10; Canada: 6; Croatia: 5; Greece: 6; India: 26; Italy: 10; Japan: 8; Republic of Korea: 4; Malaysia: 8; Mexico: 7; Poland: 8; Romania: 4; Russian Federation: 20; South Africa: 15; Spain: 6; Thailand: 6; United Kingdom: 8; United States: 271.

Participant milestones

Measure	Insulin Degludec Subjects received insulin degludec (IDeg) 100 units/mL once daily (OD) subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with insulin aspart (IAsp) at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin twice daily (BID), the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine Subjects received insulin glargine (IGlar) 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Overall Study STARTED	3818	3819
Overall Study Exposed	3809	3806
Overall Study COMPLETED	3742	3747
Overall Study NOT COMPLETED	76	72

Reasons for withdrawal

Measure	Insulin Degludec Subjects received insulin degludec (IDeg) 100 units/mL once daily (OD) subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with insulin aspart (IAsp) at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin twice daily (BID), the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine Subjects received insulin glargine (IGlar) 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Overall Study Adverse event (not hypoglycaemia)	0	1
Overall Study Lost to Follow-up	4	1
Overall Study Other	70	68
Overall Study Hypoglycaemia	1	1
Overall Study Lack of glycaemic control	1	1

Baseline Characteristics

A Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Subjects With Type 2 Diabetes at High Risk of Cardiovascular Events

Baseline characteristics by cohort

Measure	Insulin Degludec n=3818 Participants Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=3819 Participants Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.	Total n=7637 Participants Total of all reporting groups
Age, Continuous	64.9 years STANDARD_DEVIATION 7.3 • n=5 Participants	65.0 years STANDARD_DEVIATION 7.5 • n=7 Participants	65.0 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	1422 Participants n=5 Participants	1437 Participants n=7 Participants	2859 Participants n=5 Participants
Sex: Female, Male Male	2396 Participants n=5 Participants	2382 Participants n=7 Participants	4778 Participants n=5 Participants
HbA1c	8.44 percentage of HbA1c STANDARD_DEVIATION 1.63 • n=5 Participants	8.41 percentage of HbA1c STANDARD_DEVIATION 1.67 • n=7 Participants	8.43 percentage of HbA1c STANDARD_DEVIATION 1.65 • n=5 Participants

PRIMARY outcome

Timeframe: From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)

Population: The analysis was based on the FAS, which included all randomised subjects.

Time from randomisation to first occurrence of an event adjudication committee (EAC)-confirmed 3-component major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction, or nonfatal stroke. Events with EAC-confirmed onset date between randomisation and individual end of trial were included in the analyses. The number of subjects experiencing first EAC-confirmed MACEs, date between randomisation to the end of trial, both days included were presented. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.

Outcome measures

Measure	Insulin Degludec n=3818 Participants Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=3819 Participants Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke Stroke (non-fatal)	68 Participants	74 Participants
Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke First EAC-confirmed MACE	325 Participants	356 Participants
Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke Myocardial infarction (non-fatal)	143 Participants	163 Participants
Time From Randomisation to First Occurrence of a Major Adverse Cardiovascular Event (MACE): Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke Cardiovascular death	114 Participants	119 Participants

SECONDARY outcome

Timeframe: From randomisation to individual end of trial (maximum patient year observation: 2.75 years)

Population: The analysis was based on the FAS, which included all randomised subjects.

Number of severe hypoglycaemic episodes from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The trial was event driven and planned to last up to a maximum of 60.5 months. The actual trial duration (time from first subject first visit to last subject last visit) was 35.6 months. The maximum trial duration for a single subject was 33.1 months.

Outcome measures

Measure	Insulin Degludec n=3818 Participants Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=3819 Participants Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Number of EAC-confirmed Severe Hypoglycaemic Episodes	280 Number of severe episodes	472 Number of severe episodes

SECONDARY outcome

Timeframe: From randomisation to individual end of trial date (maximum patient year observation: 2.75 years)

Population: The analysis was based on the FAS, which included all randomised subjects.

Occurrence of at least one EAC-confirmed severe hypoglycaemic episode within a subject from week 0 to the last assessment (up to 35.6 months). The episode of severe hypoglycaemia is an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions.

Outcome measures

Measure	Insulin Degludec n=3818 Participants Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=3819 Participants Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Occurrence of at Least One EAC Confirmed Severe Hypoglycaemic Episode Within a Subject (Yes/no)	187 Participants	252 Participants

SECONDARY outcome

Timeframe: Randomisation to 24 months

Population: The analysis was based on the FAS. The number of subjects analysed are the number of subjects with the available data after 24 months.

Mean change in HbA1c from week 0 to month 24.

Outcome measures

Measure	Insulin Degludec n=2431 Participants Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=2404 Participants Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Change in Glycosylated Haemoglobin (HbA1c)	-0.86 percentage of HbA1c Standard Deviation 1.51	-0.84 percentage of HbA1c Standard Deviation 1.57

Adverse Events

Insulin Degludec

Serious events: 1473 serious events

Other events: 0 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 1517 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Insulin Degludec n=3818 participants at risk Subjects received IDeg 100 units/mL OD S.C. (under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pre-trial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IDeg). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IDeg OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IDeg OD, and the bolus component was calculated and switched to IAsp. The trial was event driven for with a realised observation period up to 33 months.	Insulin Glargine n=3819 participants at risk Subjects received IGlar 100 units/mL OD subcutaneously (S.C.; under the skin) in the thigh, upper arm, or the abdominal wall between dinner and bedtime. Subjects continued their pretrial medication except for the basal insulin, which was replaced by investigational medicinal product (IMP; IGlar). The pre-trial bolus insulin was allowed and could be replaced with IAsp at the discretion of the investigator. For subjects previously receiving premixed/biphasic insulin the basal component was calculated and switched to IGlar OD, and the bolus insulin component to bolus insulin. For subjects previously receiving premixed/biphasic insulin BID, the total basal component was calculated, reduced by 20- 30% and switched to IGlar OD, and the bolus component was calculated and switched to IAsp. The trial was event driven with a realised observation period up to 33 months.
Infections and infestations Abdominal abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal hernia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal hernia obstructive	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Abdominal hernia repair	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal pain	0.26% 10/3818 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.26% 10/3819 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal pain upper	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Abdominal panniculectomy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abdominal sepsis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abdominal wall abscess	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Abdominal wall haematoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abdominal wall infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abscess limb	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abscess rupture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Abscess soft tissue	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Accelerated hypertension	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Accident at work	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Accidental overdose	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Acid peptic disease	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Acquired diaphragmatic eventration	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Acute abdomen	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Acute coronary syndrome	0.29% 11/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Acute endocarditis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Acute hepatic failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Acute kidney injury	1.8% 70/3818 • Number of events 79 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	2.5% 95/3819 • Number of events 110 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Acute left ventricular failure	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Acute myocardial infarction	2.6% 98/3818 • Number of events 111 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	3.0% 115/3819 • Number of events 123 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Acute prerenal failure	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.16% 6/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.63% 24/3818 • Number of events 26 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.81% 31/3819 • Number of events 35 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Acute stress disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma gastric	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal adenoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Adrenal insufficiency	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal neoplasm	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adult T-cell lymphoma/leukaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Affective disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Aggression	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Agitation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Alcohol poisoning	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Alcohol withdrawal syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Alcoholic liver disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Alcoholic pancreatitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Altered state of consciousness	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Amputation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Anaemia	0.29% 11/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.89% 34/3819 • Number of events 40 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Anaemia postoperative	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Anaesthetic complication	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Anaesthetic complication pulmonary	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Immune system disorders Anaphylactic reaction	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Immune system disorders Anaphylactic shock	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Anastomotic ulcer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Aneurysm	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Angina pectoris	0.94% 36/3818 • Number of events 37 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.3% 48/3819 • Number of events 53 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Angina unstable	2.3% 87/3818 • Number of events 94 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	2.1% 79/3819 • Number of events 93 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Angioedema	0.08% 3/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Angiopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Angioplasty	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Animal bite	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Ankle deformity	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Ankle fracture	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Anuria	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Anxiety	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Aortic aneurysm	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Aortic aneurysm repair	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Aortic stenosis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Aortic stent insertion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Aortic valve disease	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Aortic valve replacement	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Aortic valve stenosis	0.18% 7/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Aphasia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Appendicitis	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Appendix disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Arrhythmia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Arterial haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Arteriogram coronary	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Arteriosclerosis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Arteriosclerosis coronary artery	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Arteriosclerotic gangrene	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Arteriospasm coronary	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Arteriovenous fistula operation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Arthralgia	0.13% 5/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Arthritis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Arthritis bacterial	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Arthropathy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Ascites	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Asthenia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Asthma	0.16% 6/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Asthma-chronic obstructive pulmonary disease overlap syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Ataxia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrial fibrillation	1.2% 47/3818 • Number of events 55 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.5% 56/3819 • Number of events 75 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrial flutter	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrial tachycardia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrioventricular block	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrioventricular block complete	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrioventricular block first degree	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrioventricular block second degree	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Atrioventricular dissociation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Autoimmune haemolytic anaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Azotaemia	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma stage III	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Back disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Back pain	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bacteraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bacterial infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bacterial pyelonephritis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bacterial sepsis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Balance disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Balanoposthitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Barrett's oesophagus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of bladder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.24% 9/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Beta haemolytic streptococcal infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct adenocarcinoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Bile duct stone	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Biliary dyskinesia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Biopsy lung	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Bipolar disorder	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer recurrent	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer stage 0, with cancer in situ	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Bladder neck obstruction	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Bladder outlet obstruction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma recurrent	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma stage I	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Blindness	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood creatine phosphokinase increased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood creatinine increased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood glucose decreased	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood glucose increased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood magnesium decreased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood potassium decreased	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood potassium increased	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Blood pressure inadequately controlled	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Blood pressure increased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bowen's disease	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Brachial plexus injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Bradycardia	0.21% 8/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Brain injury	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Brain stem haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Brain stem infarction	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Brain stem stroke	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage I	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage II	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer stage IV	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Breast enlargement	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bronchitis	0.42% 16/3818 • Number of events 17 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.55% 21/3819 • Number of events 21 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bronchitis bacterial	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Bronchitis viral	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Bundle branch block left	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Bundle branch block right	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Burns third degree	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Calculus bladder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Calculus urinary	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Cardiac ablation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac arrest	0.68% 26/3818 • Number of events 26 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.52% 20/3819 • Number of events 21 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Cardiac complication associated with device	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Cardiac death	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac discomfort	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac failure	0.63% 24/3818 • Number of events 26 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.79% 30/3819 • Number of events 33 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac failure acute	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac failure chronic	0.21% 8/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.26% 10/3819 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac failure congestive	3.5% 134/3818 • Number of events 177 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	3.7% 143/3819 • Number of events 206 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac hypertrophy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Cardiac monitoring	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Cardiac pacemaker battery replacement	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Cardiac pacemaker insertion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Cardiac pacemaker replacement	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cardiac valve fibroelastoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Cardiac valve replacement complication	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiac ventricular thrombosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardio-respiratory arrest	0.31% 12/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiogenic shock	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiomegaly	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiomyopathy	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiopulmonary failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiorenal syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cardiovascular disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Carotid artery disease	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Carotid artery occlusion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Carotid artery stenosis	0.39% 15/3818 • Number of events 15 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.37% 14/3819 • Number of events 15 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Cataract	0.24% 9/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Cataract diabetic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Cataract operation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Catheter site haematoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Catheter site infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Catheterisation cardiac	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cellulitis	1.4% 52/3818 • Number of events 64 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.6% 61/3819 • Number of events 72 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cellulitis orbital	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cellulitis staphylococcal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cellulitis streptococcal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebellar infarction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebral arteriosclerosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebral haemorrhage	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebral infarction	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebral ischaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebral small vessel ischaemic disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cerebrovascular accident	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.58% 22/3819 • Number of events 23 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Cervical cyst	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cervical myelopathy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Cervical spinal stenosis	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Cervix haemorrhage uterine	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Chest discomfort	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Chest pain	0.42% 16/3818 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.55% 21/3819 • Number of events 22 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Chest wall abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholangiocarcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Cholangitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Cholecystitis	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Cholecystitis acute	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Cholecystitis chronic	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cholecystitis infective	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Cholelithiasis	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Chordae tendinae rupture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Choroid melanoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Chronic gastritis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Chronic hepatic failure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Chronic kidney disease	0.42% 16/3818 • Number of events 18 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.68% 26/3819 • Number of events 30 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Chronic left ventricular failure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 42/3818 • Number of events 54 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.5% 56/3819 • Number of events 70 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Chronic respiratory failure	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Clavicle fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Clostridium difficile colitis	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Clostridium difficile infection	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Coagulation time prolonged	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Coagulopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Colectomy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Colitis	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Colitis ischaemic	0.08% 3/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage III	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Colonic abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Colostomy closure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Completed suicide	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Complication associated with device	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Concussion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Confusional state	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Congenital ureterocele	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Congestive cardiomyopathy	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Conjunctivitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Constipation	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Contusion	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Coombs negative haemolytic anaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cor pulmonale	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Cor pulmonale acute	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Coronary arterial stent insertion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Coronary artery bypass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery disease	2.1% 80/3818 • Number of events 85 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	2.3% 89/3819 • Number of events 91 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery dissection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery embolism	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery insufficiency	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery occlusion	0.31% 12/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Coronary artery restenosis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary artery stenosis	0.31% 12/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Coronary ostial stenosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Coronary vascular graft occlusion	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Costochondritis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Cough	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Cranial nerve paralysis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Craniocerebral injury	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Crohn's disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Cyst	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Cystitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Cystitis noninfective	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Cystocele	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Dactylitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Deafness neurosensory	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Death	0.71% 27/3818 • Number of events 27 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.55% 21/3819 • Number of events 21 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Decreased appetite	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Deep vein thrombosis	0.34% 13/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.26% 10/3819 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Dehydration	0.60% 23/3818 • Number of events 23 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.42% 16/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Delirium	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Dementia	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Dengue fever	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Depression	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Depression suicidal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Dermal cyst	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Dermatitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Dermatitis infected	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device dislocation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device fastener issue	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device inappropriate shock delivery	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device lead damage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device loosening	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Device malfunction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Device related infection	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Diabetes mellitus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Diabetic complication	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Diabetic foot	0.26% 10/3818 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.29% 11/3819 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Diabetic foot infection	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Diabetic gangrene	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diabetic gastroparesis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.37% 14/3819 • Number of events 14 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Diabetic metabolic decompensation	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Diabetic mononeuropathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Diabetic nephropathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Diabetic neuropathic ulcer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Diabetic neuropathy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Diabetic retinopathy	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diarrhoea	0.29% 11/3818 • Number of events 14 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Diastolic dysfunction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma recurrent	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Dilatation intrahepatic duct acquired	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Disseminated cryptococcosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diverticular perforation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Diverticulitis	0.29% 11/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.37% 14/3819 • Number of events 14 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diverticulum	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diverticulum intestinal	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Dizziness	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Drug administration error	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Immune system disorders Drug hypersensitivity	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Dry gangrene	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Duodenal stenosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Duodenal switch	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Duodenal ulcer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Duodenal vascular ectasia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Duodenitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Dysarthria	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Dysentery	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Dysphagia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.45% 17/3819 • Number of events 19 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea paroxysmal nocturnal	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Eczema	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Eczema infected	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Ejection fraction decreased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Electrocardiogram ST segment abnormal	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Electrocardiogram ST segment elevation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Electrocardiogram ST-T change	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Electrolyte imbalance	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Embolic cerebral infarction	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Embolic stroke	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Embolism	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Embolism arterial	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Embolism venous	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Empyema	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Encephalopathy	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders End stage renal disease	0.31% 12/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Endocarditis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Endometrial hyperplasia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Enteritis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Enterocele	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Enthesopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Epidural lipomatosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Epigastric discomfort	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Epiglottitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Erosive duodenitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Erysipelas	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Escherichia sepsis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Escherichia urinary tract infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Essential hypertension	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Essential tremor	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Evans syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Exostosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations External ear cellulitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Extra dose administered	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Extradural abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Extremity necrosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Eye injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Facial paralysis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Factor V deficiency	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Failure to thrive	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Fall	1.4% 54/3818 • Number of events 57 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.4% 55/3819 • Number of events 59 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Fatigue	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Femur fracture	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Flank pain	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Fluid overload	0.10% 4/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Foot deformity	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Foot fracture	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Foreign body reaction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Gait disturbance	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder adenocarcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Gangrene	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.34% 13/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Gas gangrene	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Gastrectomy	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastric antral vascular ectasia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Gastric bypass	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastric perforation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastric ulcer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastric ulcer perforation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastritis	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastritis erosive	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastroduodenitis haemorrhagic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Gastroenteritis	0.34% 13/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Gastroenteritis Escherichia coli	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Gastroenteritis viral	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Gastrointestinal anastomotic leak	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastrointestinal angiodysplasia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.26% 10/3818 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.39% 15/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Gastrointestinal injury	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal tract adenoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.16% 6/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Gastrostomy tube site complication	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Generalised oedema	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Generalised tonic-clonic seizure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Glaucoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Glomerulonephritis rapidly progressive	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Goitre	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Gout	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Graft infection	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Groin abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Guillain-Barre syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations H1N1 influenza	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Haematochezia	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Haematuria	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Haemolytic anaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Haemorrhage intracranial	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Haemorrhagic arteriovenous malformation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Haemorrhagic cerebral infarction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Haemorrhagic stroke	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Haemorrhagic transformation stroke	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Haemorrhoids	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Hallucination, visual	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Hand fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Headache	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Heart valve incompetence	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Helicobacter gastritis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hemiparesis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hemiplegic migraine	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatic cirrhosis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hepatic encephalopathy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Hepatic enzyme increased	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatic failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatic lesion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatitis chronic active	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatorenal failure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Hepatorenal syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Hernia repair	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Herpes zoster	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Hiatus hernia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Hidradenitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Hip arthroplasty	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Hip fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Humerus fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hydrocephalus	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Hydronephrosis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hyperammonaemia	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hyperglycaemia	0.29% 11/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.42% 16/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hyperglycaemic seizure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hyperkalaemia	0.47% 18/3818 • Number of events 21 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.58% 22/3819 • Number of events 24 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Hypersensitivity vasculitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Hypertension	0.45% 17/3818 • Number of events 19 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.60% 23/3819 • Number of events 24 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Hypertensive cardiomyopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Hypertensive crisis	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Hypertensive emergency	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypertensive encephalopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Hypertensive heart disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Hypertrophic cardiomyopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypoaesthesia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Hypochromic anaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hypoglycaemia	1.7% 64/3818 • Number of events 77 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.3% 49/3819 • Number of events 66 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypoglycaemic coma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypoglycaemic seizure	0.08% 3/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypoglycaemic unconsciousness	0.71% 27/3818 • Number of events 29 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.76% 29/3819 • Number of events 33 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hypokalaemia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hypomagnesaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hyponatraemia	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Hypotension	0.37% 14/3818 • Number of events 14 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.37% 14/3819 • Number of events 15 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Hypothyroidism	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Hypovolaemia	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Hypovolaemic shock	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Hysterectomy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders IIIrd nerve paralysis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Idiopathic pulmonary fibrosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Ileus	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Ileus paralytic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Ilium fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Impaired gastric emptying	0.10% 4/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Impaired healing	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Implantable defibrillator insertion	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Implantable defibrillator replacement	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Incarcerated incisional hernia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Incision site haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Incision site infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Incisional hernia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infected bite	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infected dermal cyst	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infected seroma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infected skin ulcer	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infectious colitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Influenza	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Infusion site infection	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Inguinal hernia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Inguinal hernia repair	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Inner ear disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Intensive care unit acquired weakness	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Intentional overdose	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Intentional self-injury	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Intermittent claudication	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations International normalised ratio increased	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Intervertebral disc operation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.24% 9/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Intervertebral discitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Intestinal ischaemia	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Intestinal obstruction	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Intestinal perforation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Intra-abdominal haematoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Intra-ocular injection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Intracardiac thrombus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Intracranial aneurysm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Intracranial pressure increased	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Iron deficiency anaemia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ischaemic cardiomyopathy	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Ischaemic cerebral infarction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Ischaemic hepatitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Ischaemic limb pain	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Ischaemic stroke	1.1% 43/3818 • Number of events 44 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.2% 45/3819 • Number of events 50 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Jaundice	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Jaundice cholestatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Jejunostomy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Joint abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Joint arthroplasty	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Joint dislocation	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Joint effusion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Klebsiella sepsis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Knee arthroplasty	0.10% 4/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Knee operation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Labyrinthitis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Laceration	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Lactic acidosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Lacunar infarction	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Lacunar stroke	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Large intestinal haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Large intestinal ulcer haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Large intestine polyp	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Laryngeal stenosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Product Issues Lead dislodgement	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Left ventricular dysfunction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Left ventricular failure	0.16% 6/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Left ventricular hypertrophy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Leg amputation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Leriche syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Lethargy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Leukocytosis	0.08% 3/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Ligament rupture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Limb injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Liver abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Liver disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Local swelling	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Localised infection	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Long QT syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Loss of consciousness	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Lower limb fracture	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Lower respiratory tract infection	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Lumbar radiculopathy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.31% 12/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma metastatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage II	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma stage IV	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Lyme disease	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Lymphocele	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Macular fibrosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Major depression	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Malignant hypertension	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant peritoneal neoplasm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Mallory-Weiss syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Medical device site haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Medical observation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Memory impairment	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Meniere's disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma benign	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Meningitis aseptic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Meningitis viral	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Meniscus injury	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Mental status changes	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Mesenteric haematoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mesothelioma malignant	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Metabolic acidosis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Metabolic encephalopathy	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Metabolic surgery	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic squamous cell carcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Microangiopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Migraine	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Migraine-triggered seizure	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Mitral valve incompetence	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Mononeuropathy multiplex	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Motor neurone disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mucinous endometrial carcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Mucormycosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Multiple fractures	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Multiple organ dysfunction syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Multiple sclerosis relapse	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Muscle spasms	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Muscle strain	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Muscular weakness	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Myasthenia gravis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Myocardial infarction	1.3% 48/3818 • Number of events 51 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.7% 66/3819 • Number of events 68 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Myocardial ischaemia	0.18% 7/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Nausea	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Neck pain	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Necrotising fasciitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Nephrogenic anaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Nephrolithiasis	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Nephropathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Nephropathy toxic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Nephrosclerosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Nephrotic syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Nerve root compression	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma metastatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Neuropathic ulcer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Neuropathy peripheral	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Neurotrophic keratopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Neutropenia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Neutropenic colitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Nodal arrhythmia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Non-alcoholic steatohepatitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Non-cardiac chest pain	1.2% 47/3818 • Number of events 48 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.4% 54/3819 • Number of events 63 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Non-cardiogenic pulmonary oedema	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer stage I	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Normal pressure hydrocephalus	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Normochromic normocytic anaemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Obesity	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Obstructive shock	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Oedema	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Oedema due to cardiac disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Oedema peripheral	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Oesophageal candidiasis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Oesophageal rupture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Oesophageal ulcer haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Oesophagectomy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Oesophagitis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Optic ischaemic neuropathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Oral candidiasis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Orchitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Orthostatic hypotension	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Osteitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.84% 32/3818 • Number of events 35 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.79% 30/3819 • Number of events 31 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Osteogenesis imperfecta	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Osteomyelitis	0.52% 20/3818 • Number of events 26 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.58% 22/3819 • Number of events 23 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Osteomyelitis acute	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Osteomyelitis chronic	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Osteopenia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Osteoporosis	0.03% 1/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Otitis externa	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Otitis media chronic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer recurrent	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer stage IV	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Ovarian cyst	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Overdose	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Pain	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Pain in extremity	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Palpitations	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma stage IV	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Pancreatic mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Pancreatitis	0.18% 7/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Pancreatitis acute	0.16% 6/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.29% 11/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Pancreatitis chronic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary cystadenoma lymphomatosum	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Paraesthesia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Paranoia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Paraspinal abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Parkinson's disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Paronychia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Pemphigoid	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penile squamous cell carcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Peptic ulcer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Peptic ulcer perforation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Pericardial effusion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Pericarditis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Perineal abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Periodontal disease	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral arterial occlusive disease	0.34% 13/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral artery aneurysm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral artery occlusion	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral artery stenosis	0.05% 2/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral artery thrombosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral embolism	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral ischaemia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Peripheral sensory neuropathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Peripheral swelling	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral vascular disorder	0.29% 11/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.37% 14/3819 • Number of events 17 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Peripheral venous disease	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Perirectal abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Peritoneal abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Peritonitis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Peritonitis bacterial	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Personality change due to a general medical condition	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Phaeochromocytoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pharyngeal oedema	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pharyngitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Congenital, familial and genetic disorders Phimosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Phlebitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pickwickian syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pilonidal cyst	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Pneumatosis intestinalis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia	2.4% 90/3818 • Number of events 99 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	2.4% 90/3819 • Number of events 102 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia bacterial	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia influenzal	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia klebsiella	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia mycoplasmal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia pneumococcal	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia pseudomonal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia staphylococcal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia streptococcal	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pneumonia viral	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Pneumothorax traumatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Polyarthritis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Polyp	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Portal vein thrombosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Post concussion syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Post procedural cellulitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Post procedural complication	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Post procedural haematoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Post procedural infection	0.21% 8/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Post procedural myocardial infarction	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Post procedural sepsis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Post stroke depression	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Post-injection delirium sedation syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Post-traumatic stress disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Postoperative abscess	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Postoperative fever	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Postoperative ileus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Postoperative respiratory failure	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Postoperative thoracic procedure complication	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Postoperative wound complication	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Postoperative wound infection	0.29% 11/3818 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Presyncope	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 12 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Prinzmetal angina	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Procedural complication	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Procedural hypotension	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Procedural intestinal perforation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage I	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer stage II	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Prostate infection	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Prostatitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Prostatitis Escherichia coli	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Pseudarthrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Pseudohyponatraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pseudomonal bacteraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Psychotic disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Pterygium	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Pulmonary contusion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.39% 15/3818 • Number of events 15 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.26% 10/3819 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary sarcoidosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pulmonary sepsis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary veno-occlusive disease	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Pulseless electrical activity	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pyelonephritis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.29% 11/3819 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pyelonephritis acute	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Pyrexia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Pyuria	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Radicular pain	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Radiculopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Radius fracture	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Rash	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Rectal abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenocarcinoma	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal adenoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer metastatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Rectal haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Rectal ulcer haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Rectocele	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Renal abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal artery stenosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer metastatic	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal colic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal failure	0.37% 14/3818 • Number of events 14 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.45% 17/3819 • Number of events 17 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal impairment	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Immune system disorders Renal transplant failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Renal tubular necrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Reperfusion injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.58% 22/3818 • Number of events 23 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.47% 18/3819 • Number of events 19 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Respiratory syncytial virus bronchitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Respiratory tract infection	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Respiratory tract infection viral	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Respiratory tract inflammation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Restrictive cardiomyopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Retinal artery occlusion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Retinal detachment	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Retinal vein occlusion	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Retinopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Retinopathy proliferative	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Reversible ischaemic neurological deficit	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Rib fracture	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Right ventricular failure	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Road traffic accident	0.52% 20/3818 • Number of events 21 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.47% 18/3819 • Number of events 18 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Rotator cuff repair	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Roux loop conversion	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Salivary gland calculus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Salivary gland mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Salpingitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Schizoaffective disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Schizoaffective disorder bipolar type	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Schizophrenia	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Sciatica	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Seizure	0.16% 6/3818 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Senile dementia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Sepsis	0.94% 36/3818 • Number of events 37 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.81% 31/3819 • Number of events 31 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Sepsis pasteurella	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Sepsis syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Septic arthritis staphylococcal	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Septic embolus	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Septic shock	0.29% 11/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Seroma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Shock haemorrhagic	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Sialoadenitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Silent myocardial infarction	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Sinus arrest	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Sinus bradycardia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Sinus node dysfunction	0.16% 6/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Sinus tachycardia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Sinusitis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Skin necrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Skin ulcer	0.34% 13/3818 • Number of events 13 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Skin ulcer haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer extensive stage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Small intestinal obstruction	0.24% 9/3818 • Number of events 10 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.16% 6/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Social circumstances Social stay hospitalisation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Soft tissue infection	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Soft tissue necrosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Soft tissue sarcoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Sphincter of Oddi dysfunction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Spigelian hernia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Spinal compression fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Spinal cord compression	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Spinal decompression	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Spinal fusion surgery	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Spinal laminectomy	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Spondylitic myelopathy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Spondylitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the tongue	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Stab wound	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Stag horn calculus	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Staphylococcal abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Staphylococcal infection	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Staphylococcal sepsis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Status epilepticus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Hepatobiliary disorders Steatohepatitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Stoma site reaction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Streptococcal bacteraemia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Streptococcal sepsis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Stress cardiomyopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Stress fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Stress urinary incontinence	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Subarachnoid haemorrhage	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Subclavian steal syndrome	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Subcutaneous abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Subdiaphragmatic abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Subdural haematoma	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Subdural haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Sudden cardiac death	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Sudden death	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Sudden hearing loss	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Suicidal ideation	0.13% 5/3818 • Number of events 6 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Psychiatric disorders Suicide attempt	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Superior vena cava stenosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Supraventricular tachycardia	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Surgical failure	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Syncope	0.65% 25/3818 • Number of events 27 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.63% 24/3819 • Number of events 29 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Systemic inflammatory response syndrome	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Systolic dysfunction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Tachyarrhythmia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Tachycardia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Temporal arteritis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Tendon disorder	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Tendon rupture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Tendonitis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Testicular seminoma (pure) stage I	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Testis cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Thalamic infarction	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Thalamus haemorrhage	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Thermal burn	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Blood and lymphatic system disorders Thrombocytopenia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Thrombosis	0.10% 4/3818 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Thrombotic stroke	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Thyroid mass	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Thyroidectomy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Tibia fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tonsil cancer	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Tooth abscess	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Toxic encephalopathy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Toxic goitre	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Endocrine disorders Toxic nodular goitre	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Toxicity to various agents	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Tracheobronchitis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Transfusion-related acute lung injury	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Transient global amnesia	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Transient ischaemic attack	0.73% 28/3818 • Number of events 29 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	1.1% 42/3819 • Number of events 44 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Transurethral prostatectomy	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Traumatic haematoma	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Tremor	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Tricuspid valve incompetence	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Trifascicular block	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Troponin increased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Tuberculosis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour of ampulla of Vater	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Ulnar nerve palsy	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Umbilical hernia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Surgical and medical procedures Umbilical hernia repair	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.21% 8/3819 • Number of events 8 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Upper respiratory tract infection	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Ureteric injury	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Ureterolithiasis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Urethral stenosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Urinary hesitation	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Renal and urinary disorders Urinary retention	0.24% 9/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Urinary tract infection	0.89% 34/3818 • Number of events 37 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.79% 30/3819 • Number of events 37 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Urinary tract infection bacterial	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Urosepsis	0.26% 10/3818 • Number of events 11 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.24% 9/3819 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Skin and subcutaneous tissue disorders Urticaria	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Uterine mass	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Uterine prolapse	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders VIth nerve paralysis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Varices oesophageal	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Vascular dementia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Vascular headache	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Vascular disorders Vascular insufficiency	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Vascular procedure complication	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Vascular stent restenosis	0.08% 3/3818 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Vascular stent stenosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
General disorders Vascular stent thrombosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ventricular arrhythmia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ventricular extrasystoles	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ventricular fibrillation	0.16% 6/3818 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.13% 5/3819 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ventricular hypokinesia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Cardiac disorders Ventricular tachycardia	0.21% 8/3818 • Number of events 9 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.31% 12/3819 • Number of events 16 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Musculoskeletal and connective tissue disorders Vertebral foraminal stenosis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Vertigo	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Vertigo positional	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Viraemia	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Viral infection	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.08% 3/3819 • Number of events 3 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Viral pericarditis	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Nervous system disorders Visual field defect	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Visual impairment	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Eye disorders Vitreous haemorrhage	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Gastrointestinal disorders Vomiting	0.13% 5/3818 • Number of events 5 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.18% 7/3819 • Number of events 7 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Vulval abscess	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.03% 1/3819 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Investigations Weight decreased	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Wound	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Infections and infestations Wound infection	0.05% 2/3818 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.10% 4/3819 • Number of events 4 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/3818 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.05% 2/3819 • Number of events 2 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.
Injury, poisoning and procedural complications Wrong drug administered	0.03% 1/3818 • Number of events 1 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.	0.00% 0/3819 • The adverse events were considered from the randomisation visit (week 0) to the follow up visit (end of treatment plus at least 30 days). The trial was event driven and planned to last up to a maximum of 60.5 months. The maximum trial duration for a single subject was 33.1 months. Safety was summarised using the FAS, which included all randomised subjects.

Other adverse events

Adverse event data not reported

Additional Information

Global Clinical Registry (GCR, 1452)

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee "At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property"
• Publication restrictions are in place

Restriction type: OTHER