Trial Outcomes & Findings for Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic VTE(Venous Thromboembolism) (NCT NCT02064439)

NCT ID: NCT02064439

Last Updated: 2017-12-19

Results Overview

The primary efficacy outcomes (i.e., recurrent venous thromboembolism \[VTE\] defined as composite of fatal or non-fatal symptomatic recurrent VTE, including unexplained death for which pulmonary embolism \[PE\] could not be ruled out) as confirmed by the central independent adjudication committee (CIAC) were considered up to the end of the individual intended duration of treatment. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 3365 participants
• Primary outcome timeframe: Up to 12 months, at least 6 months
• Results posted on: 2017-12-19

Participant Flow

In total 3439 participants were screened at 244 sites in 31 countries from 05-Mar-2014 (First Patient First Visit) to 15-Mar-2016 (Last Patient First Visit).

Of the 3439 participants screened 43 did not complete screening. Thus, 3396 participants were randomly assigned to treatment, 31 of the randomized participants never received study medication because either withdrew consent or were withdrawn from the study based on protocol violations.

Participant milestones

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Overall Study STARTED	1127	1107	1131
Overall Study COMPLETED	984	969	949
Overall Study NOT COMPLETED	143	138	182

Reasons for withdrawal

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Overall Study Adverse Event	51	47	46
Overall Study Death	0	2	3
Overall Study Withdrawal by Subject	29	18	26
Overall Study Protocol Violation	3	5	3
Overall Study Lost to Follow-up	1	3	4
Overall Study Non-compliance with study medication	21	19	23
Overall Study Physician Decision	0	1	1
Overall Study Logistical difficulties	6	5	2
Overall Study Efficacy outcome reached	18	16	57
Overall Study Safety outcome reached	12	20	10
Overall Study Other	2	2	7

Baseline Characteristics

Reduced-dosed Rivaroxaban in the Long-term Prevention of Recurrent Symptomatic VTE(Venous Thromboembolism)

Baseline characteristics by cohort

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 Participants Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Total n=3365 Participants Total of all reporting groups
Age, Continuous	58.8 years STANDARD_DEVIATION 14.7 • n=5 Participants	57.9 years STANDARD_DEVIATION 14.7 • n=7 Participants	58.8 years STANDARD_DEVIATION 14.7 • n=5 Participants	58.5 years STANDARD_DEVIATION 14.7 • n=4 Participants
Sex: Female, Male Female	507 Participants n=5 Participants	505 Participants n=7 Participants	488 Participants n=5 Participants	1500 Participants n=4 Participants
Sex: Female, Male Male	620 Participants n=5 Participants	602 Participants n=7 Participants	643 Participants n=5 Participants	1865 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	31 Participants n=7 Participants	30 Participants n=5 Participants	92 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	892 Participants n=5 Participants	899 Participants n=7 Participants	889 Participants n=5 Participants	2680 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	204 Participants n=5 Participants	177 Participants n=7 Participants	212 Participants n=5 Participants	593 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Asian	161 Participants n=5 Participants	159 Participants n=7 Participants	159 Participants n=5 Participants	479 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Race (NIH/OMB) Black or African American	41 Participants n=5 Participants	49 Participants n=7 Participants	36 Participants n=5 Participants	126 Participants n=4 Participants
Race (NIH/OMB) White	786 Participants n=5 Participants	772 Participants n=7 Participants	786 Participants n=5 Participants	2344 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	135 Participants n=5 Participants	126 Participants n=7 Participants	141 Participants n=5 Participants	402 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 12 months, at least 6 months

The primary efficacy outcomes (i.e., recurrent venous thromboembolism [VTE] defined as composite of fatal or non-fatal symptomatic recurrent VTE, including unexplained death for which pulmonary embolism [PE] could not be ruled out) as confirmed by the central independent adjudication committee (CIAC) were considered up to the end of the individual intended duration of treatment.

Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 Participants Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism Composite	13 participants	17 participants	50 participants
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism Symptomatic recurrent Deep vein thrombosis (DVT)	8 participants	9 participants	29 participants
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism Death (PE)	0 participants	0 participants	1 participants
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism Death (unexplained and PE cannot be ruled out)	0 participants	2 participants	1 participants
Number of Participants With the Composite of Fatal or Non-fatal Symptomatic Recurrent Venous Thromboembolism Symptomatic recurrent PE	5 participants	6 participants	19 participants

PRIMARY outcome

Timeframe: Up to 12 months, at least 6 months

The principal safety outcome was major bleeding which was defined according to the criteria of the International Society on Thrombosis and Hemostasis (ISTH) as clinically overt bleeding and associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intra articular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death.

Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 Participants Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Number of Participants With First Treatment-emergent Major Bleeding Fatal bleeding	0 participants	1 participants	1 participants
Number of Participants With First Treatment-emergent Major Bleeding Non-fatal critical organ bleed	2 participants	4 participants	1 participants
Number of Participants With First Treatment-emergent Major Bleeding Any major bleeding	5 participants	6 participants	3 participants
Number of Participants With First Treatment-emergent Major Bleeding Non-fatal non-critical organ bleeding	3 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Up to 12 months, at least 6 months

The secondary efficacy outcome is the composite of the primary efficacy outcome, myocardial infarction (MI), ischemic stroke or non-central nervous system (CNS) systemic embolism. Incidence of the composite of the primary and secondary efficacy outcome and its components are based on the first occurrence to participant.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 Participants Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Ischemic stroke	4 participants	2 participants	2 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Composite	18 participants	19 participants	56 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Non-CNS systemic embolism	1 participants	0 participants	1 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Myocardial infarction	0 participants	1 participants	4 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Symptomatic recurrent DVT	8 participants	9 participants	29 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Symptomatic recurrent PE	5 participants	6 participants	18 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Death (PE)	0 participants	0 participants	1 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Death (unexplained and PE cannot be ruled out)	0 participants	1 participants	1 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Death (cardiovascular: myocardial infarction)	0 participants	0 participants	0 participants
Number of Participants With the Composite of the Primary Efficacy Outcome, Myocardial Infarction, Ischemic Stroke or Systemic Non-CNS Embolism Death (cardiovascular: ischemic stroke)	0 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: Up to 12 months, at least 6 months

The secondary safety outcome was clinically relevant non-major (CRNM) bleeding, which was adjudicated by the CIAC using the ASA criteria: the bleeding was non-major and the bleeding was associated with a study medication interruption of more than 14 days.

Outcome measures

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 Participants Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 Participants Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Number of Participants With Non-major Bleeding Associated With Study Drug Interruption for > 14 Days	12 participants	17 participants	12 participants

Adverse Events

Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD

Serious events: 78 serious events

Other events: 40 other events

Deaths: 0 deaths

Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD

Serious events: 82 serious events

Other events: 35 other events

Deaths: 0 deaths

Acetylsalicylic (ASA) 100 mg, OD

Serious events: 79 serious events

Other events: 38 other events

Deaths: 0 deaths

Serious adverse events

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 participants at risk Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 participants at risk Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 participants at risk Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Blood and lymphatic system disorders Anaemia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Atrial fibrillation	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Atrial flutter	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Atrioventricular block second degree	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Bradycardia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Cardiac failure	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Cardiac failure chronic	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Cardiac failure congestive	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Coronary artery disease	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Mitral valve incompetence	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Myocardial ischaemia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Pericarditis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Pericarditis constrictive	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Cardiac disorders Tachycardia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Ear and labyrinth disorders Vertigo	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Ear and labyrinth disorders Vestibular disorder	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Endocrine disorders Cushing's syndrome	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Eye disorders Corneal degeneration	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Ascites	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Diverticulum	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Diverticulum intestinal	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Gastritis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Haemorrhoids	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Inguinal hernia	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Pancreatitis relapsing	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Umbilical hernia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Subileus	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Hypertrophic anal papilla	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Abdominal hernia	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Eosinophilic oesophagitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Colon dysplasia	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
General disorders Chest pain	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Hepatobiliary disorders Bile duct stone	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Hepatobiliary disorders Biliary colic	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Hepatobiliary disorders Cholecystitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Hepatobiliary disorders Cholelithiasis	0.09% 1/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Immune system disorders Overlap syndrome	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Appendicitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Cellulitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Clostridium difficile colitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Diarrhoea infectious	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Diverticulitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Erysipelas	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Gastroenteritis	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Influenza	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Nasopharyngitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Orchitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Peritonitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Plasmodium falciparum infection	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pneumonia	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.45% 5/1107 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pseudomembranous colitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pyelitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pyelonephritis acute	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Sepsis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Septic shock	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Urethral abscess	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Urinary tract infection	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.36% 4/1107 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Wound infection	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Urosepsis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Abscess limb	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Arthritis bacterial	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pseudomonal sepsis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Pneumonia bacterial	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Lung infection	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Borrelia infection	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Post procedural infection	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Ankle fracture	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Clavicle fracture	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Fall	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Femoral neck fracture	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Head injury	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Humerus fracture	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Injury	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Joint dislocation	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Overdose	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Tibia fracture	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Lower limb fracture	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Stomal hernia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Pubis fracture	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Injury, poisoning and procedural complications Craniocerebral injury	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Investigations Cystoscopy	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Investigations Haemoglobin decreased	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Investigations White blood cell count decreased	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Investigations B-lymphocyte count increased	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Metabolism and nutrition disorders Obesity	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Joint ankylosis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Osteitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.27% 3/1127 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.44% 5/1131 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Mobility decreased	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Meniscal degeneration	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Spinal pain	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign gastric neoplasm	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer recurrent	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma recurrent	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyosarcoma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified stage IV	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma stage I	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma stage IV	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lymph nodes	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma stage 0	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Plasma cell myeloma	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal cancer recurrent	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer metastatic	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.27% 3/1127 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix warts	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant glioma	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer stage IV	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Axonal neuropathy	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Dizziness	0.09% 1/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Dyskinesia	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Headache	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Migraine	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Presyncope	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Sciatica	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Seizure	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Syncope	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Facial paresis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Adjustment disorder with depressed mood	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Alcohol abuse	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Alcoholism	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Anxiety	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Depression	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Paranoia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Psychiatric disorders Suicide attempt	0.27% 3/1127 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Nephrolithiasis	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Neurogenic bladder	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Renal colic	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Renal failure	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Urinary retention	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Tubulointerstitial nephritis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Urethral stenosis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Acute kidney injury	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders End stage renal disease	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Renal and urinary disorders Ureterolithiasis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Reproductive system and breast disorders Prostatitis	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Nasal polyps	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Respiratory, thoracic and mediastinal disorders Organising pneumonia	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Seborrhoea	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Urticaria	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Cutaneous lupus erythematosus	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Surgical and medical procedures Hysterectomy	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Surgical and medical procedures Meningioma surgery	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Aortic aneurysm	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Aortic dissection	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Aortic stenosis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1107 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Hypertension	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Hypertensive crisis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Thrombophlebitis	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Vascular disorders Peripheral arterial occlusive disease	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.

Other adverse events

Measure	Rivaroxaban (Xarelto, BAY59-7939) 10 mg, OD n=1127 participants at risk Participants were randomized, stratified by country and by index event, to receive rivaroxaban 10 mg tablet or matching placebo once daily (OD) with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Rivaroxaban (Xarelto, BAY59-7939) 20 mg, OD n=1107 participants at risk Participants were randomized, stratified by country and by index event, to receive rivaroxaban 20 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.	Acetylsalicylic (ASA) 100 mg, OD n=1131 participants at risk Participants were randomized, stratified by country and by index event, to receive ASA 100 mg tablet or matching placebo OD with food for 12, or 9 to less than 12, or 6 months depending on the date of randomization. Treatment of all participants stopped 6 months after the last participant was randomized.
Cardiac disorders Atrial fibrillation	0.53% 6/1127 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Abdominal pain upper	0.18% 2/1127 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.44% 5/1131 • Number of events 5 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Constipation	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1107 • From after start of study medication but not more than 2 days after stop of study medication.	0.62% 7/1131 • Number of events 8 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Diarrhoea	0.35% 4/1127 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.36% 4/1107 • Number of events 5 • From after start of study medication but not more than 2 days after stop of study medication.	0.09% 1/1131 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Dyspepsia	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.35% 4/1131 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.45% 5/1107 • Number of events 5 • From after start of study medication but not more than 2 days after stop of study medication.	0.53% 6/1131 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.
Gastrointestinal disorders Vomiting	0.00% 0/1127 • From after start of study medication but not more than 2 days after stop of study medication.	0.36% 4/1107 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1131 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Nasopharyngitis	0.35% 4/1127 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.00% 0/1131 • From after start of study medication but not more than 2 days after stop of study medication.
Infections and infestations Upper respiratory tract infection	0.09% 1/1127 • Number of events 1 • From after start of study medication but not more than 2 days after stop of study medication.	0.36% 4/1107 • Number of events 6 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Back pain	0.27% 3/1127 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.35% 4/1131 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.
Musculoskeletal and connective tissue disorders Myalgia	0.18% 2/1127 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.18% 2/1107 • Number of events 2 • From after start of study medication but not more than 2 days after stop of study medication.	0.35% 4/1131 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.
Nervous system disorders Dizziness	0.35% 4/1127 • Number of events 5 • From after start of study medication but not more than 2 days after stop of study medication.	0.36% 4/1107 • Number of events 4 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Pruritus	0.71% 8/1127 • Number of events 8 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.
Skin and subcutaneous tissue disorders Rash	0.44% 5/1127 • Number of events 5 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1107 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.	0.27% 3/1131 • Number of events 3 • From after start of study medication but not more than 2 days after stop of study medication.

Additional Information

Therapeutic Area Head

Bayer AG

Email: clinical-trials-contact@bayer.com

Results disclosure agreements

• Principal investigator is a sponsor employee The steering committee will be responsible for the publication and presentation strategy. All publications will be based on data released or agreed by Bayer, verified by the steering committee.
• Publication restrictions are in place

Restriction type: OTHER