Trial Outcomes & Findings for A Study of Epoetin Alfa Plus Standard Supportive Care Versus Standard Supportive Care Only in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy (NCT NCT00338286)

NCT ID: NCT00338286

Last Updated: 2018-03-19

Results Overview

Progression free survival was based in investigator-determined progressive disease (PD) and calculated from the date of randomization to the date of PD or the date of death, whichever occurred first. Participants who had not progressed and were still alive at the time of clinical cut off were censored at the last disease assessment prior to the clinical cutoff. For PD or death with a missing interval immediately preceding the event, progression-free survival (PFS) was censored at the last disease assessment prior to the missing interval. Participants who withdrew from the study (withdrawal of consent or lost to follow-up) without progression were censored at the time of the last disease assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 2098 participants
• Primary outcome timeframe: From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years)
• Results posted on: 2018-03-19

Participant Flow

Participants in safety data were grouped as treatment actually received (3 were assigned to SOC but received epoetin alfa; 2 were assigned to EPO, but received SOC) so, 1 more to EPO (1051) 1 less in SOC (1045) actually received treatment. Efficacy, safety were analyzed by 1050 (EPO), 1048 (SOC), 1051 (EPO), 1045 (SOC) respectively.

Participant milestones

Measure	Standard Supportive Care (SOC) Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	Epoetin Alfa Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Overall Study STARTED	1048	1050
Overall Study COMPLETED	815	837
Overall Study NOT COMPLETED	233	213

Reasons for withdrawal

Measure	Standard Supportive Care (SOC) Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	Epoetin Alfa Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Overall Study Withdrawal by Subject	50	54
Overall Study Lost to Follow-up	80	66
Overall Study Other	103	93

Baseline Characteristics

A Study of Epoetin Alfa Plus Standard Supportive Care Versus Standard Supportive Care Only in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy

Baseline characteristics by cohort

Measure	Standard Supportive Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.	Total n=2098 Participants Total of all reporting groups
Age, Continuous	51.8 years STANDARD_DEVIATION 10.54 • n=5 Participants	51.9 years STANDARD_DEVIATION 10.49 • n=7 Participants	51.9 years STANDARD_DEVIATION 10.51 • n=5 Participants
Sex: Female, Male Female	1048 Participants n=5 Participants	1050 Participants n=7 Participants	2098 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment ARGENTINA	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment BRAZIL	27 Participants n=5 Participants	16 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment BULGARIA	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment CHILE	11 Participants n=5 Participants	13 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment COLOMBIA	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment ECUADOR	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment GEORGIA	241 Participants n=5 Participants	200 Participants n=7 Participants	441 Participants n=5 Participants
Region of Enrollment HONG KONG	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment INDIA	211 Participants n=5 Participants	237 Participants n=7 Participants	448 Participants n=5 Participants
Region of Enrollment INDONESIA	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment MACEDONIA	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Region of Enrollment MALAYSIA	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment MEXICO	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Region of Enrollment PHILIPPINES	60 Participants n=5 Participants	54 Participants n=7 Participants	114 Participants n=5 Participants
Region of Enrollment ROMANIA	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment RUSSIA	102 Participants n=5 Participants	129 Participants n=7 Participants	231 Participants n=5 Participants
Region of Enrollment TAIWAN	19 Participants n=5 Participants	30 Participants n=7 Participants	49 Participants n=5 Participants
Region of Enrollment UKRAINE	328 Participants n=5 Participants	318 Participants n=7 Participants	646 Participants n=5 Participants
Region of Enrollment UNITED STATES OF AMERICA	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of disease progression (PD) or death, whichever occurred first (up to 8.4 years)

Population: The intent to treat (ITT) population included all participants who were randomized in either Standard of Care (SOC) or Epoetin alfa group.

Progression free survival was based in investigator-determined progressive disease (PD) and calculated from the date of randomization to the date of PD or the date of death, whichever occurred first. Participants who had not progressed and were still alive at the time of clinical cut off were censored at the last disease assessment prior to the clinical cutoff. For PD or death with a missing interval immediately preceding the event, progression-free survival (PFS) was censored at the last disease assessment prior to the missing interval. Participants who withdrew from the study (withdrawal of consent or lost to follow-up) without progression were censored at the time of the last disease assessment.

Outcome measures

Measure	Standard of Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion.	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Progression Free Survival	7.4 Months Interval 7.1 to 7.6	7.4 Months Interval 6.9 to 7.6

SECONDARY outcome

Timeframe: From randomization up to death from any cause (up to 8.4 years)

Population: The intent to treat (ITT) population included all participants who were randomized in either Standard of Care (SOC) or Epoetin alfa group.

Overall survival (OS) was defined as the interval between the date of randomization to the date of death from any cause. For participants who were lost to follow-up or withdrew before the final database lock, OS was censored at the last date the participants was known to be alive. For participants who were still alive and on study at the time of the final database lock, OS was censored at the date of final database lock.

Outcome measures

Measure	Standard of Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion.	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Overall Survival	18.0 Months Interval 16.6 to 19.6	17.8 Months Interval 16.6 to 19.1

SECONDARY outcome

Timeframe: From date of randomization to the date of the first documented PD (up to 8.4 years)

Population: The intent to treat (ITT) population included all participants who were randomized in either Standard of Care (SOC) or Epoetin alfa group.

The Time to tumor progression (TTP) was defined as the time from the date of starting treatment until the date of first documented evidence of progression of tumor. TTP was measured from the date of randomization to the date of the first documented PD (including death due to PD without prior PD).

Outcome measures

Measure	Standard of Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion.	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Time to Tumor Progression	7.5 Months Interval 7.4 to 8.0	7.5 Months Interval 7.4 to 7.9

SECONDARY outcome

Timeframe: every 8 weeks for 1 year and then every 12 weeks until PD or death, whichever occurred first (up to 8.4 years)

Population: The intent to treat (ITT) population included all participants who were randomized in either Standard of Care (SOC) or Epoetin alfa group.

Overall response was RECIST criteria. Complete response (CR) is appearance of all target and non-target lesions. Partial response (PR):a) 30% decrease in sum of lactate dehydrogenase(LD) of target lesions from baseline OR b) complete disappearance of target lesions, with persistence of one or more non-target measurable lesion or one or more non-measurable, evaluable lesions. Progressive disease(PD):a) 20% increase in sum of LDs of target lesions, taking as reference smallest sum LD recorded since treatment started; OR b) appearance of one or more new lesions or a clear worsening of measurable non-target lesions or evaluable disease with stable measurable lesions. Stable disease (SD):a) sufficient shrinkage to qualify for PR;b) sufficient increase to qualify for PD. Non evaluable(NE) lesion: all other lesions, including small lesions (longest diameter <20 millimeter (mm) with conventional techniques or <10 mm with spiral CT scan) and truly non-measurable lesions.

Outcome measures

Measure	Standard of Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion.	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Overall Response Rate (ORR) Complete response (CR)	3 Percentage of participants	3 Percentage of participants
Overall Response Rate (ORR) Partial response (PR)	48 Percentage of participants	47 Percentage of participants
Overall Response Rate (ORR) Stable disease (SD)	30 Percentage of participants	32 Percentage of participants
Overall Response Rate (ORR) Progressive disease (PD)	13 Percentage of participants	12 Percentage of participants
Overall Response Rate (ORR) Not evaluable (NE)	1 Percentage of participants	2 Percentage of participants
Overall Response Rate (ORR) Not available (NA)	5 Percentage of participants	5 Percentage of participants

SECONDARY outcome

Timeframe: up to 8.4 years

Population: The intent to treat (ITT) population included all participants who were randomized in either Standard of Care (SOC) or Epoetin alfa group.

Suspected TVEs were identified by investigators and relevant clinical information was collected.

Outcome measures

Measure	Standard of Care (SOC) n=1048 Participants Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion.	Epoetin Alfa n=1050 Participants Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Percentage of Participants With Suspected Thrombotic Vascular Events (TVEs)	3.72 Percentage of participants	4.86 Percentage of participants

Adverse Events

Standard Supportive Care (SOC)

Serious events: 229 serious events

Other events: 883 other events

Deaths: 0 deaths

Epoetin Alfa

Serious events: 251 serious events

Other events: 898 other events

Deaths: 0 deaths

Serious adverse events

Measure	Standard Supportive Care (SOC) n=1045 participants at risk Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	Epoetin Alfa n=1051 participants at risk Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Vascular disorders Hypertension	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Hypotension	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.48% 5/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Hypovolaemic Shock	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Phlebitis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Shock	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Superior Vena Cava Syndrome	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Vena Cava Thrombosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Venous Thrombosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Agranulocytosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Anaemia	1.4% 15/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.95% 10/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Bone Marrow Failure	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Febrile Neutropenia	2.8% 29/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	3.8% 40/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Leukopenia	0.86% 9/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.95% 10/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Neutropenia	5.3% 55/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	4.9% 52/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Neutrophilia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Pancytopenia	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.67% 7/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 12/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	1.7% 18/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Acute Myocardial Infarction	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Arrhythmia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Arteriosclerosis Coronary Artery	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Atrial Fibrillation	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Arrest	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Disorder	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Failure	0.48% 5/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Failure Acute	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Failure Chronic	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiac Tamponade	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardio-Respiratory Arrest	0.48% 5/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiopulmonary Failure	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cardiovascular Insufficiency	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Cyanosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Left Ventricular Dysfunction	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Left Ventricular Failure	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Myocarditis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Palpitations	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Pericardial Effusion	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Sinus Tachycardia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Cardiac disorders Tachycardia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Ear and labyrinth disorders Vertigo	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Eye disorders Amaurosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Eye disorders Retinal Artery Thrombosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Eye disorders Vision Blurred	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Abdominal Discomfort	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Abdominal Distension	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Abdominal Pain	0.38% 4/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.38% 4/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Ascites	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Constipation	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Diarrhoea	1.6% 17/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	1.2% 13/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Dyspepsia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Dysphagia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Enteritis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Gastrointestinal Toxicity	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Haematochezia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Haemorrhoids	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Jejunal Perforation	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Lower Gastrointestinal Haemorrhage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Mouth Ulceration	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Nausea	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Oral Pain	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Pancreatitis Acute	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Peptic Ulcer	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Proctitis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Stomatitis	0.38% 4/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Vomiting	1.1% 11/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.86% 9/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Abasia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Asthenia	0.86% 9/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.76% 8/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Chest Discomfort	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Chest Pain	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Death	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.67% 7/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Disease Progression	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Facial Pain	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Fatigue	0.38% 4/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.38% 4/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Generalised Oedema	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Malaise	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Mucosal Inflammation	0.48% 5/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Multiple Organ Dysfunction Syndrome	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Non-Cardiac Chest Pain	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Oedema Peripheral	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Pain	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Peripheral Swelling	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Pyrexia	0.86% 9/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.95% 10/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Sudden Death	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Acute Hepatic Failure	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Cholecystitis Acute	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Cholecystitis Chronic	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hepatic Failure	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hepatic Lesion	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hepatitis Toxic	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hepatomegaly	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hepatorenal Syndrome	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Jaundice	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Hepatobiliary disorders Jaundice Hepatocellular	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Abdominal Infection	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Amoebiasis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Appendicitis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Biliary Sepsis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Breast Abscess	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Breast Cellulitis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Bronchitis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Bronchopulmonary Aspergillosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Candida Infection	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Cellulitis	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Device Related Infection	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Fungal Infection	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Gastroenteritis	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Groin Abscess	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Hepatitis Viral	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Herpes Zoster	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Infectious Pleural Effusion	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Injection Site Abscess	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Lower Respiratory Tract Infection	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Lung Infection	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Mastitis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Neutropenic Infection	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Neutropenic Sepsis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Oropharyngeal Candidiasis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Peritonitis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Plasmodium Falciparum Infection	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Pneumonia	1.1% 11/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	1.1% 12/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Pulmonary Tuberculosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Respiratory Tract Infection	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Respiratory Tract Infection Viral	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Sepsis	0.67% 7/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.67% 7/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Septic Shock	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Tuberculosis Gastrointestinal	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Upper Respiratory Tract Infection	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Urinary Tract Infection	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Infections and infestations Viral Infection	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Fall	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Femur Fracture	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Hip Fracture	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Radius Fracture	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Rib Fracture	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Injury, poisoning and procedural complications Road Traffic Accident	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Investigations Alanine Aminotransferase Increased	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Investigations Aspartate Aminotransferase Increased	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Investigations Biopsy Liver	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Decreased Appetite	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Dehydration	0.38% 4/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Diabetes Mellitus	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Electrolyte Imbalance	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Failure to Thrive	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hyperglycaemia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hypocalcaemia	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hypokalaemia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hyponatraemia	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.38% 4/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Back Pain	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Muscular Weakness	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Myalgia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Neck Pain	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in Jaw	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Soft Tissue Necrosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix Carcinoma	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphangiosis Carcinomatosa	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant Pleural Effusion	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Central Nervous System	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.95% 10/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Liver	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to Meninges	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to the Respiratory System	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oncologic Complication	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Rectal Adenocarcinoma	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour Haemorrhage	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine Leiomyoma	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Altered State of Consciousness	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Brain Oedema	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Central Nervous System Haemorrhage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Cerebral Haemorrhage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Cerebral Infarction	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Cerebrovascular Accident	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Depressed Level of Consciousness	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Diabetic Hyperglycaemic Coma	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Dizziness	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Dysarthria	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Encephalopathy	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Haemorrhage Intracranial	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Haemorrhagic Cerebral Infarction	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Headache	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.38% 4/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hemiparesis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hemiplegia	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hepatic Encephalopathy	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hydrocephalus	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hypoaesthesia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Hypoxic-Ischaemic Encephalopathy	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Iiird Nerve Paralysis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Incoherent	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Intracranial Pressure Increased	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Ischaemic Stroke	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Loss of Consciousness	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Monoparesis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Neuropathy Peripheral	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Paraesthesia	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Peripheral Motor Neuropathy	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Peripheral Sensorimotor Neuropathy	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Seizure	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.38% 4/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Somnolence	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Vertebral Artery Thrombosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Product Issues Device Breakage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Psychiatric disorders Abnormal Behaviour	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Psychiatric disorders Confusional State	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Psychiatric disorders Depressed Mood	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Psychiatric disorders Mental Status Changes	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Psychiatric disorders Schizophrenia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Renal and urinary disorders Acute Kidney Injury	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Renal and urinary disorders Renal Failure	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Renal and urinary disorders Urinary Retention	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Reproductive system and breast disorders Breast Mass	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Reproductive system and breast disorders Ovarian Cyst Torsion	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Reproductive system and breast disorders Pelvic Pain	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Reproductive system and breast disorders Uterine Polyp	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Acute Pulmonary Oedema	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Distress Syndrome	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.29% 3/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Alveolitis Allergic	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Aspiration	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Asthma	0.19% 2/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.5% 16/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	1.8% 19/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Haemothorax	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Orthopnoea	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	1.3% 14/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	1.2% 13/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.29% 3/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary Artery Thrombosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.57% 6/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.48% 5/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary Haemorrhage	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary Infarction	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Pulmonary Thrombosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory Acidosis	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory Arrest	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.38% 4/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Restrictive Pulmonary Disease	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Blister	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Dermatitis Exfoliative	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Intertrigo	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Palmar-Plantar Erythrodysaesthesia Syndrome	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Petechiae	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Skin Lesion	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.10% 1/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Stevens-Johnson Syndrome	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Deep Vein Thrombosis	0.00% 0/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.19% 2/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Vascular disorders Haemorrhage	0.10% 1/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	0.00% 0/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.

Other adverse events

Measure	Standard Supportive Care (SOC) n=1045 participants at risk Participants received standard supportive care as packed red blood cells (RBC) transfusion as per Investigator's discretion	Epoetin Alfa n=1051 participants at risk Participants received SOC plus epoetin alfa 40,000 international units (IU) subcutaneously (SC) once a week.
Blood and lymphatic system disorders Anaemia	14.6% 153/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	9.3% 98/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Leukopenia	26.7% 279/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	25.7% 270/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Neutropenia	52.6% 550/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	50.4% 530/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Blood and lymphatic system disorders Thrombocytopenia	9.3% 97/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	9.0% 95/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Constipation	3.8% 40/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	5.0% 53/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Diarrhoea	18.1% 189/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	17.1% 180/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Dry Mouth	4.4% 46/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	5.4% 57/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Nausea	22.2% 232/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	24.5% 257/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Stomatitis	7.6% 79/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	6.8% 71/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Gastrointestinal disorders Vomiting	10.8% 113/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	9.4% 99/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Asthenia	13.3% 139/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	12.5% 131/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Fatigue	20.6% 215/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	19.1% 201/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Oedema Peripheral	7.8% 81/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	6.9% 73/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
General disorders Pyrexia	11.0% 115/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	11.5% 121/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Investigations Alanine Aminotransferase Increased	6.4% 67/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	6.8% 71/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Investigations Aspartate Aminotransferase Increased	6.3% 66/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	7.3% 77/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Metabolism and nutrition disorders Decreased Appetite	18.2% 190/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	17.3% 182/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Arthralgia	7.8% 81/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	5.3% 56/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Back Pain	5.2% 54/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	5.2% 55/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Musculoskeletal and connective tissue disorders Pain in Extremity	5.6% 59/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	6.3% 66/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Dysgeusia	5.4% 56/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	7.0% 74/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Headache	7.1% 74/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	8.5% 89/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Neuropathy Peripheral	7.1% 74/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	7.9% 83/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Nervous system disorders Peripheral Sensory Neuropathy	10.6% 111/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	9.2% 97/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Cough	9.1% 95/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	11.6% 122/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.1% 74/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	7.3% 77/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.
Skin and subcutaneous tissue disorders Alopecia	31.2% 326/1045 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.	29.9% 314/1051 • From randomization up to 8.4 years The Safety analysis set included included all randomized participants for whom safety assessment data were available. Participants in the safety population were grouped according to the treatment actually received.

Additional Information

Director, Clinical Research

Janssen Research and Development

Email: ClinicalTrialDisclosure@its.jnj.com

Results disclosure agreements

• Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
• Publication restrictions are in place

Restriction type: OTHER