Trial Outcomes & Findings for Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A) (NCT NCT00249873)

NCT ID: NCT00249873

Last Updated: 2015-06-15

Results Overview

The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up : * stroke (nonfatal or fatal) * myocardial infarction (nonfatal or fatal) * non-CNS systemic embolism * vascular death The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 7554 participants
• Primary outcome timeframe: expected median follow-up of approximately 3 years
• Results posted on: 2015-06-15

Participant Flow

Patients were enrolled from June 2003 until May 2006. The study was conducted at 580 centers in 33 countries. The planned final follow-up visit date ensuring a median follow-up of three years was November 2008. The follow-up of the study was actually completed on March 2009 corresponding to an actual median follow-up of 3.5 years.

Participant milestones

Measure	Clopidogrel + ASA Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Overall Study STARTED	3772	3782
Overall Study COMPLETED	2442	2528
Overall Study NOT COMPLETED	1330	1254

Reasons for withdrawal

Measure	Clopidogrel + ASA Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Overall Study Not treated	7	8
Overall Study Significant thrombocytopenia	9	8
Overall Study Severe allergic reaction	8	1
Overall Study Serious haemorrhagic Adverse Event	74	30
Overall Study Other Serious Adverse Event	86	97
Overall Study Qualifying condition not present	20	23
Overall Study Contraindication to oral anticoagulant	4	8
Overall Study Withdrawal by Subject	504	466
Overall Study Lost to Follow-up	4	7
Overall Study Minor bleeding	99	37
Overall Study Non-compliance	41	46
Overall Study Other non serious Adverse Event	112	108
Overall Study Other contraindicated medication	1	0
Overall Study Patient not wish to continue after May08	3	4
Overall Study Physician withdrew consent	59	60
Overall Study Open label clopidogrel required	31	42
Overall Study Angiotensin II receptor blocker required	1	0
Overall Study Oral anticoagulant required	159	157
Overall Study Study drug intolerance	5	0
Overall Study Surgery/ procedure	9	9
Overall Study Event related to cardiac condition	12	21
Overall Study Thromboembolic/outcome event	82	122

Baseline Characteristics

Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events (ACTIVE A)

Baseline characteristics by cohort

Measure	Clopidogrel + ASA n=3772 Participants Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 Participants Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)	Total n=7554 Participants Total of all reporting groups
Age, Customized 18 to <65 years	931 participants n=5 Participants	935 participants n=7 Participants	1866 participants n=5 Participants
Age, Customized 65 to <75 years	1291 participants n=5 Participants	1258 participants n=7 Participants	2549 participants n=5 Participants
Age, Customized >= 75 years	1550 participants n=5 Participants	1589 participants n=7 Participants	3139 participants n=5 Participants
Age, Continuous	70.9 years STANDARD_DEVIATION 10.2 • n=5 Participants	71.1 years STANDARD_DEVIATION 10.2 • n=7 Participants	71.0 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	1560 Participants n=5 Participants	1597 Participants n=7 Participants	3157 Participants n=5 Participants
Sex: Female, Male Male	2212 Participants n=5 Participants	2185 Participants n=7 Participants	4397 Participants n=5 Participants
CHADS2 Score 0	105 participants n=5 Participants	101 participants n=7 Participants	206 participants n=5 Participants
CHADS2 Score 1	1360 participants n=5 Participants	1338 participants n=7 Participants	2698 participants n=5 Participants
CHADS2 Score 2	1263 participants n=5 Participants	1315 participants n=7 Participants	2578 participants n=5 Participants
CHADS2 Score >2	1040 participants n=5 Participants	1028 participants n=7 Participants	2068 participants n=5 Participants
CHADS2 Score Missing	4 participants n=5 Participants	0 participants n=7 Participants	4 participants n=5 Participants
Sitting Systolic Blood Pressure <120 mmHg	603 participants n=5 Participants	620 participants n=7 Participants	1223 participants n=5 Participants
Sitting Systolic Blood Pressure >=120 mmHg	3166 participants n=5 Participants	3159 participants n=7 Participants	6325 participants n=5 Participants
Sitting Systolic Blood Pressure Missing	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Body Mass Index (BMI)	28.370 kg/m² STANDARD_DEVIATION 5.575 • n=5 Participants	28.459 kg/m² STANDARD_DEVIATION 6.022 • n=7 Participants	28.415 kg/m² STANDARD_DEVIATION 5.803 • n=5 Participants

PRIMARY outcome

Timeframe: expected median follow-up of approximately 3 years

Population: The intent-to-treat (ITT) population was used for all analyses. This consisted of all randomized patients irrespective of whether or not the patient actually received study drug or the patient's compliance with the study protocol. All patients were included in the treatment group to which they were originally allocated.

The primary event is the first occurence of any adjudicated component of the following cluster over the duration of follow-up :

• stroke (nonfatal or fatal)
• myocardial infarction (nonfatal or fatal)
• non-CNS systemic embolism
• vascular death

The primary efficacy analysis is performed on the time from randomization to this primary event. Numbers of patients with the composite event over the duration of the follow-up are presented by arm group.

Outcome measures

Measure	Clopidogrel + ASA n=3772 Participants Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 Participants Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication - Myocardial Infarction (fatal or not)	84 participants	105 participants
First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication All components	832 participants	924 participants
First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication - Stroke (fatal or not)	285 participants	391 participants
First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication - Non-CNS systemic embolism	50 participants	48 participants
First Occurence of Any Component of the Composite of Stroke, Non-Central Nervous System (Non-CNS) Systemic Embolism, Myocardial Infarction or Vascular Death as Per Adjudication - Vascular death	413 participants	380 participants

SECONDARY outcome

Timeframe: expected median follow-up of approximately 3 years

Population: The intent-to-treat (ITT) population was used for this analysis.

The event is the occurence of stroke (nonfatal or fatal, ischemic, hemorrhagic or of uncertain type) after validation of the Event Adjudication Committee . The analysis is performed on the time from randomization to the occurrence of this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

Outcome measures

Measure	Clopidogrel + ASA n=3772 Participants Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 Participants Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Occurrence of Stroke	296 participants	408 participants

SECONDARY outcome

Timeframe: expected median follow-up of approximately 3 years

Population: The intent-to-treat (ITT) population was used for the analysis.

The considered event is death from any cause. The analysis is performed on the time from randomization to this event. Numbers of patients with the event over the duration of the follow-up are presented by arm group.

Outcome measures

Measure	Clopidogrel + ASA n=3772 Participants Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 Participants Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Death From Any Cause (Cardiovascular and Noncardiovascular)	825 participants	841 participants

SECONDARY outcome

Timeframe: expected median follow-up of approximately 3 years

Population: The intent-to-treat (ITT) population was used for the analysis.

The number of participants with at least one major bleeding, validated by the Event Adjudication Committee are counted over the duration of the follow-up (including after permanent discontinuation of the study drug).

Outcome measures

Measure	Clopidogrel + ASA n=3772 Participants Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 Participants Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Adjudicated Major Bleedings	251 participants	162 participants

Adverse Events

Clopidogrel + ASA

Serious events: 1154 serious events

Other events: 2542 other events

Deaths: 0 deaths

Placebo + ASA

Serious events: 1069 serious events

Other events: 2502 other events

Deaths: 0 deaths

Serious adverse events

Measure	Clopidogrel + ASA n=3772 participants at risk Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 participants at risk Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Blood and lymphatic system disorders Anaemia	0.48% 18/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.50% 19/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Anaemia megaloblastic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Anaemia of chronic disease	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Anaemia of malignant disease	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Haemorrhagic disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Hypochromic anaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Iron deficiency anaemia	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Nephrogenic anaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Pancytopenia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Blood and lymphatic system disorders Thrombocytopenia	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Angina pectoris	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Atrial fibrillation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Atrioventricular block complete	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Bradycardia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Cardiac amyloidosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Cardiopulmonary failure	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Intracardiac thrombus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Pericardial haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Pericarditis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Sinoatrial block	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Tricuspid valve disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Adenomatous polyposis coli	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Dermoid cyst	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia haemorrhagic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Hydrocele	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Muscular dystrophy	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Congenital, familial and genetic disorders Phimosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Deafness neurosensory	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Hearing impaired	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Vertigo	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Vertigo positional	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Ear and labyrinth disorders Vestibular disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Autoimmune thyroiditis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Diabetes insipidus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Ectopic hyperthyroidism	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Goitre	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Hyperparathyroidism	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Hyperparathyroidism secondary	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Hyperthyroidism	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Hypothyroidism	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Thyroiditis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Endocrine disorders Toxic nodular goitre	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Angle closure glaucoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Cataract	0.53% 20/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.48% 18/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Corneal degeneration	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Diplopia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Eye haemorrhage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Eyelid oedema	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Glaucoma	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Maculopathy	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Pupils unequal	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Retinal artery occlusion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Retinal degeneration	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Retinal detachment	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Retinal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Retinal vein thrombosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Visual impairment	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Abdominal hernia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Abdominal pain	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Abdominal pain upper	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Abdominal strangulated hernia	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Acute abdomen	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Anal fissure	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Appendicitis perforated	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Barrett's oesophagus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Coeliac disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Colitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Colitis ischaemic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Colitis ulcerative	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Colonic polyp	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Colonic stenosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Constipation	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diarrhoea	0.29% 11/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diarrhoea haemorrhagic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diverticular perforation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diverticulitis intestinal haemorrhagic	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diverticulum	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diverticulum intestinal	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Diverticulum intestinal haemorrhagic	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Duodenal ulcer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Duodenal ulcer perforation	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Duodenitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Dyspepsia	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Dysphagia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Enterocolitis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Enterocolitis haemorrhagic	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Faecaloma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Femoral hernia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Femoral hernia, obstructive	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Food poisoning	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gallstone ileus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric antral vascular ectasia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric haemorrhage	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric mucosal lesion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric polyps	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric ulcer	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.56% 21/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastritis	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastritis erosive	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastritis haemorrhagic	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastroduodenal ulcer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastroduodenitis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.69% 26/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastrointestinal necrosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastrointestinal ulcer haemorrhage	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Gastrooesophagitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Haematochezia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Haemorrhoids	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Hiatus hernia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Ileus	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Inguinal hernia	0.48% 18/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.45% 17/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Inguinal hernia, obstructive	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal dilatation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal functional disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal haemorrhage	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal infarction	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal ischaemia	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal obstruction	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal perforation	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal polyp	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intestinal strangulation	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intra-abdominal haematoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Intra-abdominal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Irritable bowel syndrome	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Large intestinal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Large intestine perforation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.34% 13/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Mallory-weiss syndrome	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Mechanical ileus	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Melaena	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Mesenteric occlusion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Nausea	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophageal perforation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophageal ulcer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophageal ulcer haemorrhage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophagitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Oesophagitis haemorrhagic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Pancreatitis	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Pancreatitis acute	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Pancreatitis chronic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Peptic ulcer	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Peptic ulcer haemorrhage	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Periodontitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Peritoneal adhesions	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Peritonitis	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Rectal haemorrhage	0.27% 10/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Rectal polyp	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Rectal prolapse	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Reflux oesophagitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Retroperitoneal haematoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Retroperitoneal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Salivary gland calculus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Small intestinal obstruction	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Stomatitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Subileus	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Tooth disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Umbilical hernia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Umbilical hernia, obstructive	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.74% 28/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Volvulus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Vomiting	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Asthenia	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Chest pain	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Cyst	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Death	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Dysplasia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Fatigue	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Gait disturbance	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders General physical health deterioration	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Generalised oedema	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Hernia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Malaise	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Multi-organ failure	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Non-cardiac chest pain	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Oedema peripheral	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Pelvic mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Perforated ulcer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Performance status decreased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Puncture site haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Pyrexia	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Submandibular mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Swelling	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Alcoholic liver disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Bile duct stone	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Biliary cirrhosis primary	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Biliary colic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholangitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholangitis acute	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholecystitis	0.42% 16/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.32% 12/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholecystitis acute	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholecystitis chronic	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholelithiasis	0.42% 16/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.48% 18/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cholestasis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Cirrhosis alcoholic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic cirrhosis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic congestion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic cyst	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic failure	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic function abnormal	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatic mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatitis acute	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatitis alcoholic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatitis toxic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hepatocellular injury	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Jaundice	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Hepatobiliary disorders Post cholecystectomy syndrome	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Immune system disorders Drug hypersensitivity	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Immune system disorders Hypersensitivity	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Abdominal sepsis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Abscess	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Abscess neck	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Acarodermatitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations American trypanosomiasis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Anogenital warts	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Appendiceal abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Appendicitis	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Arthritis bacterial	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Arthritis infective	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bacteraemia	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bacterial infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Biliary tract infection	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Breast abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bronchiectasis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bronchitis	0.53% 20/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.34% 13/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bronchitis viral	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Bronchopneumonia	0.27% 10/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.40% 15/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Cellulitis	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Central line infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Chronic sinusitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Clostridial infection	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Clostridium difficile colitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Corneal abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Cryptosporidiosis infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Cystitis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Dengue fever	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Dermo-hypodermitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Device related infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Diverticulitis	0.29% 11/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Emphysematous cholecystitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Empyema	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Endocarditis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Endocarditis bacterial	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Enterocolitis infectious	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Erysipelas	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Escherichia infection	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gallbladder empyema	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gangrene	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gastroenteritis	0.34% 13/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gastroenteritis norovirus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gastroenteritis salmonella	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gastroenteritis viral	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Gastrointestinal infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Groin abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Haematoma infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Hepatitis e	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Herpes zoster	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Herpes zoster ophthalmic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Implant site infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Infected skin ulcer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Infection	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Influenza	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Intervertebral discitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Keratitis fungal	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Labyrinthitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Lobar pneumonia	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Localised infection	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Lower respiratory tract infection	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Lower respiratory tract infection viral	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Lung infection	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Meningitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Nasopharyngitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Necrotising fasciitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Orchitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Osteomyelitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Otitis externa	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Otitis media	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Parotitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Perirectal abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Peritoneal infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pharyngitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pilonidal cyst	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumococcal infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumonia	3.7% 139/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	3.4% 128/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumonia klebsiella	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumonia primary atypical	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumonia staphylococcal	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pneumonia streptococcal	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Portal pyaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Post procedural infection	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Post procedural sepsis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Postoperative wound infection	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pseudomonas infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pulmonary sepsis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pulmonary tuberculosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pyelonephritis	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Pyelonephritis acute	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Renal abscess	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Respiratory tract infection	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Sepsis	0.72% 27/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.50% 19/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Sepsis syndrome	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Septic shock	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Sinusitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Skin bacterial infection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Staphylococcal infection	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Staphylococcal sepsis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Staphylococcal toxaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Streptococcal sepsis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Subcutaneous abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Tetanus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Thrombophlebitis septic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Tooth abscess	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Toxic shock syndrome	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Tracheobronchitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Tuberculosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Upper respiratory tract infection	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Urethritis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Urinary tract infection	0.61% 23/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.74% 28/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Urosepsis	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Viral infection	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Viral pericarditis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Vulval abscess	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Wound infection	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Infections and infestations Wound infection staphylococcal	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Accidental overdose	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Alcohol poisoning	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Anaemia postoperative	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Anastomotic leak	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Anastomotic stenosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Anastomotic ulcer haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Ankle fracture	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Asbestosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Brain contusion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Concussion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Contusion	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Dislocation of joint prosthesis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Drug toxicity	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Ear injury	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Epiphyseal fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Extradural haematoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Facial bones fracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Fall	0.64% 24/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.50% 19/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Femoral neck fracture	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Femur fracture	0.40% 15/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.50% 19/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Foot fracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Fracture displacement	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Fractured coccyx	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Fractured sacrum	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Graft complication	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Haematuria traumatic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Head injury	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Heat exhaustion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Hip fracture	0.32% 12/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.48% 18/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Humerus fracture	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Implantable defibrillator malfunction	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Injury	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Joint dislocation	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Joint injury	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Joint sprain	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Limb injury	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Muscle rupture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Open fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Open wound	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Operative haemorrhage	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Overdose	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Pacemaker complication	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Patella fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Pelvic fracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Pharyngeal injury	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Poisoning	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Post procedural complication	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Post procedural haematoma	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Post procedural haematuria	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.27% 10/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Post-traumatic pain	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Postoperative adhesion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Postoperative ileus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Postoperative renal failure	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Procedural pain	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Pubic rami fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Radiation mucositis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Radius fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Rib fracture	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Delusional disorder, persecutory type	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Road traffic accident	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Scapula fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Skin laceration	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Spinal compression fracture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Spinal fracture	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Subcutaneous haematoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Subdural haematoma	0.37% 14/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Subdural haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Tendon injury	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Tendon rupture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Therapeutic agent toxicity	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Thermal burn	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Thoracic vertebral fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Tibia fracture	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Traumatic brain injury	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Traumatic haematoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Traumatic haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Traumatic intracranial haemorrhage	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Upper limb fracture	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Wound	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Wound complication	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Wrist fracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Aspiration bronchial	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Carbohydrate tolerance decreased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Haemoglobin decreased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations International normalised ratio increased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Prostatic specific antigen increased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Weight decreased	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Cachexia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Dehydration	0.50% 19/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.34% 13/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Electrolyte imbalance	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Failure to thrive	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Gout	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Haemosiderosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hyperkalaemia	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hypoalbuminaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hypoglycaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hypokalaemia	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hyponatraemia	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Hypovolaemia	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Malnutrition	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Metabolic disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Obesity	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Starvation	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Underweight	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Arthritis	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Back pain	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Bunion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Bursitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Dupuytren's contracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Finger deformity	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Foot deformity	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Mobility decreased	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.74% 28/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.95% 36/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Osteochondrosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Osteoporosis	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Pain in extremity	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Periarthritis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Periostitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Polymyalgia rheumatica	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Senile osteoporosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Abdominal neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute leukaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute myeloid leukaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adrenal neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basosquamous carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign anorectal neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign lung neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of bladder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct cancer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary cancer metastatic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer recurrent	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder papilloma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone sarcoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain neoplasm malignant	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.24% 9/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.34% 13/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer female	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Carcinoid tumour of the stomach	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cholesteatoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic lymphocytic leukaemia	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.34% 13/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.29% 11/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage iv	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colorectal cancer metastatic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cystosarcoma phyllodes	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large b-cell lymphoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Duodenal neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer metastatic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gallbladder cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.27% 10/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal stromal tumour	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma multiforme	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of liver	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intestinal adenocarcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large cell carcinoma of the respiratory tract stage unspecified	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large granular lymphocytosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.29% 11/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung squamous cell carcinoma stage unspecified	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary hilum mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Peripheral ischaemia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymph node cancer metastatic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphocytic leukaemia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma in situ	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant soft tissue neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Mediastinum neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to adrenals	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic gastric cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic squamous cell carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Nasal neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm malignant	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurilemmoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma of the skin	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer stage IV	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal adenocarcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oral neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma metastatic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neoplasm	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic neuroendocrine tumour	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papilloma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pelvic neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penis carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal carcinoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pharyngeal cancer stage unspecified	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pituitary tumour benign	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasmacytoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pleural mesothelioma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.64% 24/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.42% 16/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostatic adenoma	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer metastatic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectosigmoid cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer metastatic	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland adenoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma uterus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small intestine carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of skin	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid adenoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage unspecified	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulval cancer	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Amyotrophic lateral sclerosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Ataxia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Balance disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Carpal tunnel syndrome	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cauda equina syndrome	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebral artery occlusion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebral disorder	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebral haematoma	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebral haemorrhage	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebrovascular accident	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cerebrovascular disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cervical root pain	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Cognitive disorder	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Convulsion	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Dementia	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Dementia Alzheimer's type	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Dizziness	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Dizziness postural	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Encephalitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Encephalopathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Epilepsy	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Extrapyramidal disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Facial paresis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Grand mal convulsion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Guillain-barre syndrome	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Haemorrhage intracranial	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Haemorrhagic stroke	0.45% 17/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.26% 10/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Haemorrhagic transformation stroke	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Headache	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Hydrocephalus	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Hypokinesia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Intercostal neuralgia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Intracranial haematoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Ivth nerve paralysis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Loss of consciousness	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Lumbar radiculopathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Mental impairment	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Mononeuropathy	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Nervous system disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Neuralgia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Neurological decompensation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Optic neuritis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Paraesthesia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Parkinson's disease	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Polyneuropathy	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Post herpetic neuralgia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Presyncope	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Radicular syndrome	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Sciatica	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Simple partial seizures	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Somnolence	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Spinal cord compression	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Status epilepticus	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Subarachnoid haemorrhage	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Syncope	0.32% 12/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.24% 9/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Syncope vasovagal	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Thalamus haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Thrombotic stroke	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Vascular dementia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Vascular encephalopathy	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Vertebrobasilar insufficiency	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Abnormal behaviour	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Alcohol abuse	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Alcohol withdrawal syndrome	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Alcoholism	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Bipolar i disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Completed suicide	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Confusional state	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Delirium	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Delusion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Depression	0.29% 11/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Hallucination	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Major depression	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Mental disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Mental status changes	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Neurosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Panic disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Psychotic disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Schizophrenia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Psychiatric disorders Schizophrenia, paranoid type	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Anuria	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Bladder neck sclerosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Bladder obstruction	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Bladder stenosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Calculus bladder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Calculus ureteric	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Calculus urinary	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Cystitis haemorrhagic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Cystitis noninfective	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Cystitis ulcerative	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Dysuria	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Enuresis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Glomerulonephritis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Glomerulonephritis chronic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Haematuria	0.27% 10/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Haemorrhage urinary tract	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Hydronephrosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Nephrolithiasis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Nephropathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Obstructive uropathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Polyuria	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Proteinuria	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal artery stenosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal colic	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal cyst	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal failure	0.42% 16/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.37% 14/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal failure acute	0.58% 22/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.61% 23/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal failure chronic	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.13% 5/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Renal impairment	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Ureteric obstruction	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urethral fistula	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urethral meatus stenosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urethral stenosis	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urinary bladder haemorrhage	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urinary bladder polyp	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urinary incontinence	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urinary retention	0.29% 11/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Urinary tract disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.32% 12/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.34% 13/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Breast mass	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Cervical dysplasia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Colpocele	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Endometrial atrophy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Endometrial hyperplasia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Endometrial hypertrophy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Fibrocystic breast disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Gynaecomastia	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Ovarian cyst	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Prostatic disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Prostatic haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Prostatism	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Prostatitis	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Prostatomegaly	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Rectocele	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Uterine enlargement	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Uterine haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Uterine polyp	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Uterine prolapse	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Vaginal cyst	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Reproductive system and breast disorders Vaginal haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Alveolitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Asthma	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchial disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchitis chronic	0.19% 7/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchopneumopathy	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.74% 28/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.71% 27/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.45% 17/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.19% 7/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.08% 3/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pleural adhesion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.21% 8/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.21% 8/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.11% 4/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.11% 4/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary congestion	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Thoracic haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Tonsillar disorder	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Pemphigoid	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Pustular psoriasis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Rash	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Skin induration	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Skin lesion	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Skin necrosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Skin ulcer	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Skin ulcer haemorrhage	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Stasis dermatitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Toxic skin eruption	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Urticaria	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Bedridden	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Disability	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Elderly	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Joint prosthesis user	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Social problem	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Social circumstances Social stay hospitalisation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Circumcision	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Haemorrhoid operation	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Hip arthroplasty	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Intestinal stoma	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Intraocular lens implant	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Obesity surgery	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Surgical and medical procedures Wound drainage	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Aneurysm	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Angiodysplasia	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Aortic aneurysm	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.16% 6/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Aortic aneurysm rupture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Aortic dissection	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Aortic rupture	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Arteriosclerosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Arteriosclerosis obliterans	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Bleeding varicose vein	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Cardiovascular insufficiency	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Circulatory collapse	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Deep vein thrombosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Femoral artery aneurysm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Haematoma	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Haemorrhage	0.16% 6/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Hypertension	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Hypertensive crisis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Hypotension	0.13% 5/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.08% 3/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Orthostatic hypotension	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Peripheral artery aneurysm	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Peripheral embolism	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Peripheral vascular disorder	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Thrombophlebitis	0.05% 2/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Thrombosis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Varicose ulceration	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Varicose vein	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Vasculitis	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.05% 2/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Venous insufficiency	0.03% 1/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.00% 0/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Venous thrombosis	0.00% 0/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	0.03% 1/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.

Other adverse events

Measure	Clopidogrel + ASA n=3772 participants at risk Clopidogrel 75 mg once daily (od) plus acetylsalicyclic acid (ASA) 75 to 100 mg od recommended (dose at the investigators' discretion)	Placebo + ASA n=3782 participants at risk Matching placebo of clopidogrel 75 mg od plus ASA 75 to 100 mg od recommended (dose at the investigators' discretion)
Infections and infestations Any Infections and infestations	26.4% 994/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	25.4% 961/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Gastrointestinal disorders Any Gastrointestinal disorders	21.4% 806/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	20.2% 763/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Any Nervous system disorders	17.5% 661/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	18.0% 682/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Nervous system disorders Dizziness	8.0% 300/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	8.2% 312/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
General disorders Any General disorders and administration site conditions	15.4% 582/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	14.3% 541/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Any Respiratory, thoracic and mediastinal disorders	14.3% 538/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	13.5% 510/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.1% 231/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	5.7% 215/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Musculoskeletal and connective tissue disorders Any Musculoskeletal and connective tissue disorders	14.1% 532/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	16.5% 623/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Vascular disorders Any Vascular disorders	11.7% 440/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	10.9% 414/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Injury, poisoning and procedural complications Any Injury, poisoning and procedural complications	11.5% 433/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	9.3% 353/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Skin and subcutaneous tissue disorders Any Skin and subcutaneous tissue disorders	8.9% 337/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	7.6% 289/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Cardiac disorders Any Cardiac disorders	8.0% 301/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	8.3% 314/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Metabolism and nutrition disorders Any Metabolism and nutrition disorders	6.3% 239/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	6.8% 257/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Any Neoplasms benign, malignant and unspecified (incl cysts and polyps)	5.8% 220/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	5.5% 208/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Eye disorders Any Eye disorders	5.0% 190/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	5.2% 198/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Investigations Any Investigations	4.9% 185/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	5.3% 201/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.
Renal and urinary disorders Any Renal and urinary disorders	4.9% 184/3772 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.	5.2% 196/3782 • From randomization through 28 days after the end of study drug treatment or the final follow-up visit. In both treatment groups, median duration of exposure was approximately 36 months, with a maximum of 62 months. The intent to treat population was also used for safety analyses.

Additional Information

International Clinical Development, Clinical Study Director

sanofi-aventis

Email: GV-Contact-us@sanofi-aventis.com

Results disclosure agreements

• Principal investigator is a sponsor employee Publication of the study will be made jointly in the name of all wholehearted collaborators. Other papers will be authored based on the contributions of the individuals to the overall study. Substudies with scientific merit which have received prior approval from the Steering Committee (SC) may be published in the names of the contributing investigators. A copy of all manuscripts will be provided to the sponsors for their review. The final decision to publish articles will be made by the SC.
• Publication restrictions are in place

Restriction type: OTHER