Trial Outcomes & Findings for Assessment of an Education and Guidance Programme for Eliquis Adherence in Non-Valvular Atrial Fibrillation (AEGEAN) (NCT NCT01884350)

Last Updated: 2019-08-19

Results Overview

The mean percentage of days which participants maintained adherence to apixaban treatment was measured for each arm. Adherence to apixaban = number of units of adherence \*100 / total number of eligible days for the time period from first dose date, up to 169 days. Unit of adherence: A 24-hour window where the treatment is taken as prescribed, ie, 1 tablet (5 mg or 2.5 mg, as appropriate) 2 times a day. If only one dose is missed in 24-hours, it is still considered as a unit of adherence. Adherence up to 24 weeks was calculated as the percentage of adherence units within that period. If a participant discontinued from the study before 24 weeks, the denominator time period was censored at the earlier of last dose date or discontinuation date for discontinuation due to reasons unrelated to participant adherence, such as withdrawn consent, or AE; otherwise, the period was censored at the minimum of 169 days and last dose date + 30 days.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1217 participants

Primary outcome timeframe

Day 1 up to week 24

Results posted on

2019-08-19

Participant Flow

1217 participants were enrolled, 1162 randomized (583 Primary SOC,579 AEP). 55 were enrolled but not randomized. Of the 55, 13 no longer met study criteria, 13 withdrew consent, 3 lost to follow-up, 10 other and 16 unknown.

Participant milestones

Participant milestones
Measure	Apixaban (Primary SOC) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Primary Efficacy Analysis Set (24 Weeks) STARTED	583	579	0
Primary Efficacy Analysis Set (24 Weeks) Safety Analysis Set	604	558	0
Primary Efficacy Analysis Set (24 Weeks) COMPLETED	529	525	0
Primary Efficacy Analysis Set (24 Weeks) NOT COMPLETED	54	54	0
Primary Efficacy Analysis Set (48 Weeks) STARTED	583	263	261
Primary Efficacy Analysis Set (48 Weeks) Safety Analysis Set	604	308	223
Primary Efficacy Analysis Set (48 Weeks) COMPLETED	503	250	250
Primary Efficacy Analysis Set (48 Weeks) NOT COMPLETED	80	13	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban (Primary SOC) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Primary Efficacy Analysis Set (24 Weeks) Subject Withdrew Consent	17	20	0
Primary Efficacy Analysis Set (24 Weeks) Death	6	4	0
Primary Efficacy Analysis Set (24 Weeks) Lost to Follow-up	0	1	0
Primary Efficacy Analysis Set (24 Weeks) Serious Adverse Event	7	6	0
Primary Efficacy Analysis Set (24 Weeks) Adverse Event	15	11	0
Primary Efficacy Analysis Set (24 Weeks) Drug Interruption >30 Consecutive Days	0	2	0
Primary Efficacy Analysis Set (24 Weeks) Inclusion/exclusion criterion	2	5	0
Primary Efficacy Analysis Set (24 Weeks) Helping Hand not used	2	0	0
Primary Efficacy Analysis Set (24 Weeks) Helping Hand not used, treatment taken	1	1	0
Primary Efficacy Analysis Set (24 Weeks) Withdrawal by Subject	1	1	0
Primary Efficacy Analysis Set (24 Weeks) Medical reason	3	3	0
Primary Efficacy Analysis Set (48 Weeks) Subject Withdrew Consent	21	0	2
Primary Efficacy Analysis Set (48 Weeks) Death	7	3	3
Primary Efficacy Analysis Set (48 Weeks) Lost to Follow-up	1	0	1
Primary Efficacy Analysis Set (48 Weeks) Serious Adverse Event	17	6	3
Primary Efficacy Analysis Set (48 Weeks) Adverse Event	17	3	0
Primary Efficacy Analysis Set (48 Weeks) Drug Interruption >30 Consecutive Days	3	0	2
Primary Efficacy Analysis Set (48 Weeks) Helping Hand not used	4	0	0
Primary Efficacy Analysis Set (48 Weeks) Helping Hand not used, treatment taken	3	0	0
Primary Efficacy Analysis Set (48 Weeks) Medical reason	4	1	0
Primary Efficacy Analysis Set (48 Weeks) Subject decision	1	0	0
Primary Efficacy Analysis Set (48 Weeks) Inclusion / Exclusion Criterion	2	0	0

Baseline Characteristics

Assessment of an Education and Guidance Programme for Eliquis Adherence in Non-Valvular Atrial Fibrillation (AEGEAN)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban (Primary SOC Information) n=583 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=579 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Total n=1162 Participants Total of all reporting groups
Age, Continuous	72.6 years STANDARD_DEVIATION 8.94 • n=5 Participants	73.1 years STANDARD_DEVIATION 9.05 • n=7 Participants	72.9 years STANDARD_DEVIATION 9.00 • n=5 Participants
Age, Customized <64 years	86 Participants n=5 Participants	77 Participants n=7 Participants	163 Participants n=5 Participants
Age, Customized 64-74 years	221 Participants n=5 Participants	220 Participants n=7 Participants	441 Participants n=5 Participants
Age, Customized >=75 years	276 Participants n=5 Participants	282 Participants n=7 Participants	558 Participants n=5 Participants
Sex: Female, Male Female	232 Participants n=5 Participants	234 Participants n=7 Participants	466 Participants n=5 Participants
Sex: Female, Male Male	351 Participants n=5 Participants	345 Participants n=7 Participants	696 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to week 24

Population: Primary efficacy analysis set (Week 24), which consists of all randomized participants

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=583 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=579 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen	91.64 percentage of days Standard Deviation 17.143	91.88 percentage of days Standard Deviation 16.140	—

SECONDARY outcome

Timeframe: Day 1 to Week 12, Week 12 to Week 24

Population: Primary efficacy analysis set (Week 24) with available data at both study days 85 and 169

The mean adherence to apixaban treatment during the first 24 weeks was measured between the standard of care (SOC) information and Additional Education Program (AEP) arms and expressed as a percentage. Adherence to Apixaban = number of units of adherence \*100 / total number of eligible days for the time period.

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=583 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=579 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 12 to 24 Weeks Period Compared With During the First 12 Weeks Day 1 to Week 12	93.7 percentage Standard Deviation 14.18	93.0 percentage Standard Deviation 15.71	—
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 12 to 24 Weeks Period Compared With During the First 12 Weeks Week 12 to Week 24	90.3 percentage Standard Deviation 20.64	90.9 percentage Standard Deviation 18.36	—

SECONDARY outcome

Timeframe: Week 24 to Week 48

Population: All treated participants in 24 to 48-week period. Participants that had not been using the EMD consistently throughout the study were excluded from the analysis.

The mean percentage of days which participants maintained adherence to apixaban treatment was measured for each arm. Adherence to apixaban = number of units of adherence \*100 / total number of eligible days for the time period from first dose date, up to 169 days. Unit of adherence: A 24-hour window where the treatment is taken as prescribed, ie, 1 tablet (5 mg or 2.5 mg, as appropriate) 2 times a day. If only one dose is missed in 24-hours, it is still considered as a unit of adherence. Adherence over 24 weeks was calculated as the percentage of adherence units within that period. If a participant discontinued from the study before 48 weeks, the denominator time period was censored at the earlier of last dose date or discontinuation date for discontinuation due to reasons unrelated to participant adherence, such as withdrawn consent, or AE; otherwise, the period was censored at the minimum of 169 days and last dose date + 30 days.

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=510 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=253 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) n=254 Participants Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Percentage of Days With a Correct Execution of the Apixaban Dosing Regimen During the 24 to 48 Weeks Period	87.59 percentage Standard Deviation 22.921	88.41 percentage Standard Deviation 22.148	87.51 percentage Standard Deviation 21.125

SECONDARY outcome

Timeframe: Week 24

Population: Primary Efficacy Set participants with evaluable data at week 24

Logit analyses were conducted on the Primary Efficacy Set to identify non-adherence predictors of 20% or more (vs. at least 80% adherence) at 24 weeks. In the Primary SOC group, alcohol use, Mini-Mental State Evaluation (MMSE) score, UK standard occupational classification, and type of atrial fibrillation were retained in the model (p-value \<= 0.2). In the Additional Educational Program group, alcohol use, type of atrial fibrillation, age and Vitamin K Antagonists (VKA) status were retained in the model (p-value \<= 0.2). Odds ratios are presented for predictors of non-adherence.

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=557 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=560 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks <=2 Alcoholic Drink/Day Average vs None	1.251 Odds ratio Interval 0.691 to 2.265	0.994 Odds ratio Interval 0.558 to 1.682	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks >=3 Alcoholic Drink/Day Average vs None	4.268 Odds ratio Interval 1.226 to 14.859	3.782 Odds ratio Interval 0.884 to 16.178	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Mini-mental state examination score	0.808 Odds ratio Interval 0.686 to 0.952	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Higher mgmt., adm. and professional jobs vs UKSOC1	0.827 Odds ratio Interval 0.136 to 5.033	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Higher professional occupations vs UKSOC1	0.898 Odds ratio Interval 0.197 to 4.091	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Intermediate occupations vs UKSOC1	1.230 Odds ratio Interval 0.401 to 3.769	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Large employers and mgmt. and adm. jobs vs UKSOC1	2.823 Odds ratio Interval 0.412 to 19.338	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Lower mgmt., adm. and professional jobs vs UKSOC1	0.948 Odds ratio Interval 0.256 to 3.515	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Lower supervisory and tech. occupations vs UKSOC1	3.587 Odds ratio Interval 1.008 to 12.766	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Never worked and long-term unemployed vs UKSOC1	1.289 Odds ratio Interval 0.419 to 3.962	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Routine occupations vs UKSOC1	0.508 Odds ratio Interval 0.181 to 1.425	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Semi-routine occupations vs UKSOC1	0.450 Odds ratio Interval 0.083 to 2.453	NA Odds ratio Not retained in model (p-value \> 0.2)	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Paroxysmal vs Persistant Atrial Fibrillation	1.626 Odds ratio Interval 0.766 to 3.453	1.911 Odds ratio Interval 0.94 to 3.885	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks Permanent vs Persistant Atrial Fibrillation	2.560 Odds ratio Interval 1.152 to 5.688	1.846 Odds ratio Interval 0.819 to 4.158	—
Non-adherence Predictors of 20% or More (vs. at Least 80% Adherence) at 24 Weeks VKA Naïve vs Non-Naïve	NA Odds ratio Not retained in model (p-value \> 0.2)	1.686 Odds ratio Interval 0.932 to 3.049	—

SECONDARY outcome

Timeframe: Day 1 up to week 24

Population: All randomized participants. Participants in the safety analysis set were categorized according to the counseling actually received

AEs with onset date from day 1 through week 24 are included in this summary. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=604 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=558 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death SAE	75 Participants	82 Participants	—
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death Drug related AE	54 Participants	41 Participants	—
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death AE leading to discontinuation	33 Participants	22 Participants	—
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death Death	6 Participants	5 Participants	—

SECONDARY outcome

Timeframe: Week 24 up to Week 48

Population: All randomized participants remaining in the study after week 24. All randomized participants. Participants in the safety analysis set were categorized according to the counseling actually received

Adverse events with onset date after 24 weeks are included in this summary. AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Outcome measures

Outcome measures
Measure	Apixaban (Primary SOC Information) n=604 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received Primary Standard of Care (SOC) information.	Apixaban (Additional Educational Program) n=308 Participants Participants were treated with Apixaban 2.5 mg or 5 mg by mouth twice daily for 48 weeks and received the Additional Educational Program (AEP). After the initial 24-week primary endpoint period, participants in the AEP group were randomized 1:1 to continue receiving AEP or stop receiving AEP and revert to Standard of Care (SOC) information via the Apixaban (Secondary SOC) group.	Apixaban (Secondary SOC) n=223 Participants Participants were originally in the Apixaban (AEP) arm and treated with Apixaban 2.5 mg or 5 mg by mouth twice daily and Additional Educational Program (AEP) for the first 24 weeks. After the initial 24-week primary endpoint period participants stopped receiving AEP and were transferred from Apixaban (AEP) arm, stopped the Additional Educational Program (AEP), and switched to the Standard of Care (SOC) information for an additional 24 weeks.
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death SAE	71 Participants	43 Participants	30 Participants
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death Drug related AE	15 Participants	12 Participants	10 Participants
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death AE leading to discontinuation	14 Participants	3 Participants	8 Participants
Number of Participants With Serious Adverse Events (SAEs), Drug Related Adverse Events (AE), AE Leading to Discontinuation, and Death Death	3 Participants	3 Participants	6 Participants

Adverse Events

Primary SOC (Period 1)

Serious events: 69 serious events

Other events: 40 other events

Deaths: 0 deaths

Continued Additional Educational Program (CAEP) (Period 2)

Serious events: 40 serious events

Other events: 5 other events

Deaths: 0 deaths

Secondary SOC (Period 2)

Serious events: 29 serious events

Other events: 5 other events

Deaths: 0 deaths

Additional Educational Program (Period 1)

Serious events: 79 serious events

Other events: 46 other events

Deaths: 0 deaths

Primary SOC (Period 2)

Serious events: 62 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Primary SOC (Period 1) n=604 participants at risk Apixaban 2.5 mg or 5 mg by mouth twice daily for 24 weeks and Primary SOC information.	Continued Additional Educational Program (CAEP) (Period 2) n=308 participants at risk Subjects enrolled in AEP program during the first 24 weeks continued receiving AEP program up to 48 weeks.	Secondary SOC (Period 2) n=223 participants at risk Subjects who received AEP for 24 weeks then revert to SOC after the second randomization.	Additional Educational Program (Period 1) n=558 participants at risk Apixaban 2.5 mg or 5 mg by mouth twice daily for 24 weeks and Additional Educational Program.	Primary SOC (Period 2) n=604 participants at risk Subjects who received Apixaban 2.5 mg or 5 mg by mouth twice daily for initial 24 weeks and Primary SOC information continued for a period 48 Weeks.
Vascular disorders Aneurysm ruptured	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Deep vein thrombosis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Haematoma	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Haemorrhage	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Hypertension	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.65% 2/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Hypertensive crisis	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Hypotension	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Phlebitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Vascular disorders Peripheral ischaemia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Arthroscopic surgery	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Breast conserving surgery	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cancer surgery	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cardiac ablation	1.3% 8/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.54% 3/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.50% 3/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cardiac pacemaker insertion	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cardiac pacemaker battery replacement	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cardiac resynchronisation therapy	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Cardioversion	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Corneal transplant	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Coronary angioplasty	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Coronary artery bypass	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Coronary arterial stent insertion	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Heart valve replacement	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Gastrointestinal endoscopic therapy	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Inguinal hernia repair	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Intervertebral disc operation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Knee arthroplasty	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Joint arthroplasty	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Leg amputation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Lung lobectomy	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Mitral valve replacement	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Percutaneous coronary intervention	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Nephrectomy	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Spinal operation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Scar excision	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Transurethral prostatectomy	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Surgery	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Varicose vein operation	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Surgical and medical procedures Vascular graft	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma pancreas	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder neoplasm	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchial carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive lobular breast carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic neoplasm	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer metastatic	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid neoplasm	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin cancer	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tongue neoplasm malignant stage	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Social circumstances Elderly	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Chest pain	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.50% 3/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Drug intolerance	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Device malfunction	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders General physical health deterioration	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Impaired healing	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Inflammation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Implant site haematoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Malaise	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Multi-Organ failure	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Oedema peripheral	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Pyrexia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
General disorders Sudden death	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Psychiatric disorders Sleep disorder	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Reproductive system and breast disorders Acquired phimosis	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Reproductive system and breast disorders Breast cyst	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Reproductive system and breast disorders Prostatitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Cervical vertebral fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Contusion	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Chest injury	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Fall	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.54% 3/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Head injury	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Femur fracture	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Laceration	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Injury	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Overdose	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Traumatic fracture	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Injury, poisoning and procedural complications Vascular pseudoaneurysm	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Aspiration breast	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Arteriogram coronary	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Blood test abnormal	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Biopsy lung	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Cardiac stress test abnormal	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Catheterisation cardiac	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Investigations Oxygen saturation decreased	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Acute coronary syndrome	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Angina pectoris	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.65% 2/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Angina unstable	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Aortic valve disease	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Atrial fibrillation	1.2% 7/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	1.8% 10/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.50% 3/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Arrhythmia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Atrial flutter	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Atrial tachycardia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Atrioventricular block	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Bradyarrhythmia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Bradycardia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac arrest	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac failure acute	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac failure chronic	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac failure	1.5% 9/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.97% 3/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	2.3% 13/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.66% 4/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac flutter	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac failure congestive	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Cardiac valve disease	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Left ventricular failure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Coronary artery disease	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Mitral valve incompetence	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Myocardial infarction	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.90% 2/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Myocardial ischaemia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Pericardial effusion	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Palpitations	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Sinus bradycardia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Right ventricular failure	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Tachyarrhythmia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Ventricular fibrillation	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.65% 2/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.90% 2/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.72% 4/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Blood and lymphatic system disorders Anaemia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Blood and lymphatic system disorders Hypochromic anaemia	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Blood and lymphatic system disorders Hypofibrinogenaemia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Blood and lymphatic system disorders Spontaneous haematoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Aphasia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Basal ganglia infarction	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Cerebellar haemorrhage	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Cerebrovascular accident	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Cerebral haematoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Dizziness	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Epilepsy	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Haemorrhage intracranial	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Parkinson's disease	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Hypertonia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Post stroke seizure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Multiple sclerosis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Radicular syndrome	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Seizure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Syncope	0.50% 3/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Nervous system disorders Transient ischaemic attack	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Ear and labyrinth disorders Vertigo	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Abdominal pain	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Abdominal hernia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Abdominal wall haematoma	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Barrett's oesophagus	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Diarrhoea	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Constipation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Diverticular perforation	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Gastritis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Haematochezia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Inguinal hernia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Large intestine perforation	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Intestinal haemorrhage	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Large intestine polyp	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Vomiting	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Gastrointestinal disorders Rectal polyp	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Acute kidney injury	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Cystitis haemorrhagic	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Haematuria	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Renal disorder	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Renal failure	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Renal impairment	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Renal and urinary disorders Urethral stenosis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Hepatobiliary disorders Bile duct stone	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Hepatobiliary disorders Cholecystitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Hepatobiliary disorders Hepatic lesion	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Hepatobiliary disorders Cholelithiasis	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Skin and subcutaneous tissue disorders Diabetic foot	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Skin and subcutaneous tissue disorders Skin ulcer	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Mobility decreased	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.36% 2/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Musculoskeletal and connective tissue disorders Spondylolisthesis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Appendicitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Bronchitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Diabetic gangrene	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Cellulitis	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Escherichia urinary tract infection	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Erysipelas	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.45% 1/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Helicobacter gastritis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Gangrene	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Herpes zoster	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.65% 2/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Pneumonia	0.83% 5/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.90% 2/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.54% 3/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.33% 2/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Pyelonephritis acute	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Sepsis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Respiratory tract infection	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Septic shock	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Urinary tract infection	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Streptococcal endocarditis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Vestibular neuronitis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.18% 1/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Infections and infestations Urosepsis	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.17% 1/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.
Cardiac disorders Congestive cardiomyopathy	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.32% 1/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	0.00% 0/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.

Other adverse events

Other adverse events
Measure	Primary SOC (Period 1) n=604 participants at risk Apixaban 2.5 mg or 5 mg by mouth twice daily for 24 weeks and Primary SOC information.	Continued Additional Educational Program (CAEP) (Period 2) n=308 participants at risk Subjects enrolled in AEP program during the first 24 weeks continued receiving AEP program up to 48 weeks.	Secondary SOC (Period 2) n=223 participants at risk Subjects who received AEP for 24 weeks then revert to SOC after the second randomization.	Additional Educational Program (Period 1) n=558 participants at risk Apixaban 2.5 mg or 5 mg by mouth twice daily for 24 weeks and Additional Educational Program.	Primary SOC (Period 2) n=604 participants at risk Subjects who received Apixaban 2.5 mg or 5 mg by mouth twice daily for initial 24 weeks and Primary SOC information continued for a period 48 Weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.6% 40/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	1.6% 5/308 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	2.2% 5/223 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	8.2% 46/558 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.	3.5% 21/604 • From date of first dose to date of last dose plus 30 days All randomized participants were analyzed. Participants in the safety analysis set were categorized according to the counseling actually received.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER