Trial Outcomes & Findings for LUME-Ovar 1: Nintedanib (BIBF 1120) or Placebo in Combination With Paclitaxel and Carboplatin in First Line Treatment of Ovarian Cancer (NCT NCT01015118)

NCT ID: NCT01015118

Last Updated: 2017-12-07

Results Overview

Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment. The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1366 participants
• Primary outcome timeframe: First drug administration to date of disease progression or death whichever occurs first , upto 29 months
• Results posted on: 2017-12-07

Participant Flow

1366 patients were randomised for this study.

Participant milestones

Measure	Nintedanib Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Overall Study STARTED	911	455
Overall Study COMPLETED	242	128
Overall Study NOT COMPLETED	669	327

Reasons for withdrawal

Measure	Nintedanib Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Overall Study Protocol Violation	5	6
Overall Study Withdrawal by Subject	103	27
Overall Study Other Adverse Event (AE)	141	33
Overall Study Worsening or AE of underlying disease	5	4
Overall Study Progressive disease	364	229
Overall Study Not treated	9	5
Overall Study Other than stated above	42	23

Baseline Characteristics

LUME-Ovar 1: Nintedanib (BIBF 1120) or Placebo in Combination With Paclitaxel and Carboplatin in First Line Treatment of Ovarian Cancer

Baseline characteristics by cohort

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Total n=1366 Participants Total of all reporting groups
Age, Continuous	57.5 Years STANDARD_DEVIATION 11.0 • n=5 Participants	56.9 Years STANDARD_DEVIATION 11.1 • n=7 Participants	57.3 Years STANDARD_DEVIATION 11.1 • n=5 Participants
Sex: Female, Male Female	911 Participants n=5 Participants	455 Participants n=7 Participants	1366 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: First drug administration to date of disease progression or death whichever occurs first , upto 29 months

Population: Randomised Set (RS)

Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment.

The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria.	17.2 Months Interval 11.1 to 32.5	16.6 Months Interval 10.8 to 30.4

PRIMARY outcome

Timeframe: First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

Population: Randomised Set (RS)

Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria (Follow up Analysis).	17.6 Months Interval 11.1 to 38.0	16.6 Months Interval 10.8 to 37.3

SECONDARY outcome

Timeframe: First drug administration to date of disease progression or death whichever occurs first , upto 29 months

Population: Randomised Set (RS)

Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1.

The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint).	18.3 Months Interval 11.1 to 32.5	16.6 Months Interval 10.8 to 30.4

SECONDARY outcome

Timeframe: First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

Population: Randomised Set (RS)

Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint - Follow up Analysis).	18.4 Months Interval 11.1 to 38.5	16.6 Months Interval 10.8 to 37.3

SECONDARY outcome

Timeframe: First drug administration to date of death until final DBL 26September16, upto 62 months

Population: Randomised Set (RS)

Overall survival is defined as time from randomization to date of death (irrespective of reason).

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Overall Survival	62.0 Months Interval 30.0 to Not calculable because of insufficient number of participants with events	62.8 Months Interval 30.6 to Not calculable because of insufficient number of participants with events

SECONDARY outcome

Timeframe: First drug administration until final DBL 26September16, upto 62 months

Population: Randomised set (RS)

Time to tumour-marker progression was defined as the time from randomisation until the date when Carbohydrate (cancer) antigen (CA-125) values increased to higher than twice the nadir value. CA-125 >=2 x nadir in case nadir value > Upper limit of normal (ULN) or CA-125 >=2 x ULN in case nadir value <= ULN.

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Time to CA-125 Tumour Marker Progression	16.6 Months Interval 10.6 to 47.0	14.1 Months Interval 8.6 to 42.6

SECONDARY outcome

Timeframe: First drug administration until final DBL 26September16, upto 62 months

Population: Randomised Set (RS) for patients with at least 1 target lesion reported at baseline

Objective tumour response defined as either complete response [CR] or partial response [PR] in patients with at least 1 target lesion reported at baseline

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Objective Response Based on Investigator Assessment	74.3 percentage of participants	70.2 percentage of participants

SECONDARY outcome

Timeframe: First drug administration until final DBL 26September16, upto 62 months

Population: Randomised Set (RS) for patients with abdominal/gastro-intestinal symptoms

Change in abdominal/gastro-intestinal over time was calculated on symptoms (scale composite of items 31 to 37 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Module for Ovarian Cancer 28 (EORTC QLQ OV-28).

As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/severe level of symptomatology).

Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postoperative tumour at baseline (yes vs. no), FIGO stage (IIB-III vs IV), and Carboplatin level (AUC5 vs. AUC6).

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Change in Abdominal/Gastro-intestinal Symptoms Over Time	24.63 units on a scale Standard Error 0.49	19.34 units on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: First drug administration until final DBL 26September16, upto 62 months

Population: Randomised Set (RS) for patients with global health status/QoL

Change in Global Health Status/ Quality of life (QoL) over time was calculated on Global Health Status/QoL scale (composite of items 29 and 30 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) as a general measure.

As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/healthy level of functioning).

Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postoperative tumour at baseline (yes vs. no), FIGO stage (IIB-III vs IV), and Carboplatin level (AUC5 vs. AUC6).

Outcome measures

Measure	Nintedanib n=911 Participants Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Placebo n=455 Participants Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Change in Global Health Status/ Quality of Life (QoL) Scale Over Time.	68.79 units on a scale Standard Error 0.48	70.67 units on a scale Standard Error 0.65

Adverse Events

Placebo

Serious events: 157 serious events

Other events: 442 other events

Deaths: 0 deaths

Nintedanib

Serious events: 379 serious events

Other events: 891 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=450 participants at risk Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Nintedanib n=902 participants at risk Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	1.6% 7/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.7% 15/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to large intestine	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to reproductive organ	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to small intestine	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian epithelial cancer	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary thyroid cancer	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraneoplastic syndrome	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pelvic neoplasm	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal neoplasm	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Amnesia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Asterixis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Cerebral infarction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Cerebrovascular accident	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Coma	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Dizziness	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.55% 5/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Headache	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.55% 5/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Hemianopia homonymous	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Intracranial aneurysm	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Ischaemic stroke	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Myoclonus	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Neuralgia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Neuropathy peripheral	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Paraesthesia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Peripheral sensorimotor neuropathy	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Sciatica	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Syncope	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Transient ischaemic attack	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Trigeminal neuralgia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Product Issues Device dislocation	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Product Issues Thrombosis in device	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Anxiety	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Conversion disorder	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Depression	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Hallucination	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Mental disorder	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Personality change	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Acute kidney injury	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Bladder tamponade	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Haematuria	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Hydronephrosis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.78% 7/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Incontinence	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Proteinuria	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Renal failure	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Ureteric obstruction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Ureteric stenosis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Urinary bladder haemorrhage	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Urinary retention	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Urogenital fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Renal and urinary disorders Vesicocutaneous fistula	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Cervical polyp	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Pelvic pain	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Uterine fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Vaginal fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Vaginal haemorrhage	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Vaginal prolapse	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Reproductive system and breast disorders Vaginal ulceration	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Asthma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Cough	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.89% 4/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.1% 10/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Dyspnoea at rest	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Hydrothorax	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.1% 5/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.2% 11/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Dermatomyositis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Drug eruption	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Rash	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Skin erosion	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Urticarial vasculitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Catheter placement	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Central venous catheter removal	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Chemotherapy	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Cholecystectomy	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Cytoreductive surgery	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Ileostomy	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Intestinal resection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Laparotomy	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Large intestine anastomosis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Surgical and medical procedures Vaginal operation	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Accelerated hypertension	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Aortic aneurysm	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Axillary vein thrombosis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Circulatory collapse	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Deep vein thrombosis	1.1% 5/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Haematoma	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Hypertension	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.55% 5/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Hypertensive crisis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Hypotension	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Lymphocele	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Lymphoedema	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Malignant hypertension	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Orthostatic hypotension	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Pelvic venous thrombosis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Thrombophlebitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Thrombosis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Varicose vein	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Vasculitis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Vena cava thrombosis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Venous occlusion	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Venous thrombosis limb	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Lymphadenopathy	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Anaemia	2.0% 9/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	4.0% 36/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Febrile bone marrow aplasia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Febrile neutropenia	1.3% 6/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.2% 20/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Haemolytic uraemic syndrome	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Leukopenia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.89% 8/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Microangiopathic haemolytic anaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Neutropenia	1.3% 6/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.7% 24/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Pancytopenia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.89% 8/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Splenic infarction	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Splenic vein thrombosis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Thrombocytopenia	1.3% 6/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.3% 21/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Thrombotic thrombocytopenic purpura	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Acute coronary syndrome	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Acute myocardial infarction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Angina pectoris	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Atrial fibrillation	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Atrioventricular block	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Bundle branch block left	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Cardiac arrest	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Cardiogenic shock	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Cardiovascular disorder	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Mitral valve incompetence	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Myocardial infarction	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Myocardial ischaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Palpitations	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Sinus tachycardia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Supraventricular tachyarrhythmia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Tachycardia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Cardiac disorders Ventricular tachycardia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Congenital, familial and genetic disorders Cancer gene carrier	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Ear and labyrinth disorders Deafness	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Ear and labyrinth disorders Tinnitus	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Ear and labyrinth disorders Vertigo	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Endocrine disorders Goitre	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Endocrine disorders Toxic nodular goitre	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Eye disorders Vision blurred	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal adhesions	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal discomfort	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal distension	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal hernia	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal pain	1.3% 6/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	3.3% 30/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.89% 8/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal wall haematoma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Acute abdomen	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Anal fissure	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Anal fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Anal haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Ascites	1.8% 8/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.6% 14/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Colitis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Colonic fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Constipation	2.2% 10/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.4% 13/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Diaphragmatic hernia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Diarrhoea	1.8% 8/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	4.5% 41/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Diverticulum intestinal	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Dysphagia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Enteritis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Enterocutaneous fistula	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Faecaloma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Femoral hernia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Fistula of small intestine	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Functional gastrointestinal disorder	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Gastritis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Gastrointestinal inflammation	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Gastrointestinal pain	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Haematemesis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Ileus	1.8% 8/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.9% 17/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Impaired gastric emptying	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Intestinal obstruction	0.89% 4/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.78% 7/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Intestinal perforation	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.55% 5/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Intussusception	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Large intestinal obstruction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Mallory-Weiss syndrome	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Mechanical ileus	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Nausea	2.2% 10/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.7% 24/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Pancreatitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Pancreatitis acute	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Small intestinal obstruction	0.89% 4/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.3% 12/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Small intestinal perforation	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Stomatitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Subileus	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.89% 8/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Umbilical hernia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Vomiting	2.7% 12/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	3.7% 33/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pseudomonal sepsis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Asthenia	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.4% 13/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Catheter site haematoma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Chest pain	0.89% 4/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Chills	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Cyst	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Death	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Fatigue	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.1% 10/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders General physical health deterioration	1.1% 5/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.9% 17/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Hernia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Impaired healing	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Implant site erythema	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Influenza like illness	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Infusion site extravasation	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Mucosal inflammation	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Nodule	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Oedema	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Oedema peripheral	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Pain	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Performance status decreased	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Pyrexia	1.8% 8/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.5% 23/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Sudden death	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Surgical failure	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Hepatobiliary disorders Cholecystitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Hepatobiliary disorders Cholelithiasis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Allergy to arthropod bite	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Anaphylactic reaction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Anaphylactoid reaction	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Contrast media allergy	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Drug hypersensitivity	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.00% 9/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Hypersensitivity	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Abdominal abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Abdominal wall abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Appendicitis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Bacteraemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Beta haemolytic streptococcal infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Cellulitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Clostridial infection	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Clostridium difficile colitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Clostridium difficile infection	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Cystitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Device related infection	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Diverticulitis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Endocarditis bacterial	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Enteritis infectious	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Enterobacter infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Enterocolitis bacterial	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Erysipelas	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Escherichia urinary tract infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Febrile infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Gastroenteritis	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Gastrointestinal infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Infected lymphocele	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Infection	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Infectious pleural effusion	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Joint abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Klebsiella infection	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Liver abscess	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Lung infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Mesenteric abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Nasopharyngitis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Neutropenic sepsis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pelvic abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Peritonitis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pharyngeal abscess	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pneumonia	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Postoperative abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Postoperative wound infection	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pulpitis dental	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pyelonephritis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Pyelonephritis acute	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Rectal abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Respiratory tract infection	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Sepsis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Septic shock	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Sinusitis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Subdiaphragmatic abscess	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Tooth abscess	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Upper respiratory tract infection	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Urinary tract infection	0.67% 3/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	1.9% 17/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Urinary tract infection bacterial	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Urinary tract infection enterococcal	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Urosepsis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Abdominal wound dehiscence	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Facial bones fracture	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Fall	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Femoral neck fracture	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Femur fracture	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Fibula fracture	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Fractured coccyx	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Gastrointestinal anastomotic leak	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Gastrointestinal stoma complication	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Head injury	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Humerus fracture	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Iatrogenic injury	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Incisional hernia	0.89% 4/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.89% 8/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Inflammation of wound	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Infusion related reaction	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Ligament sprain	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Meniscus injury	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Post procedural diarrhoea	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Postoperative fever	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Scar	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Stoma site haemorrhage	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Tibia fracture	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Vulvovaginal injury	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Injury, poisoning and procedural complications Wound dehiscence	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Alanine aminotransferase increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Aspartate aminotransferase increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Biopsy vulva	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Blood creatinine increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Blood glucose increased	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Body temperature increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations C-reactive protein increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Creatinine renal clearance decreased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Eastern Cooperative Oncology Group performance status worsened	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Electrocardiogram abnormal	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Fibrin D dimer increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Gamma-glutamyltransferase increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Glomerular filtration rate decreased	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Haemoglobin decreased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Lipase increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Neutrophil count decreased	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Platelet count decreased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.55% 5/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Troponin increased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Weight decreased	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations White blood cell count decreased	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.44% 4/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Dehydration	1.3% 6/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	2.3% 21/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypoalbuminaemia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypokalaemia	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.67% 6/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypovolaemia	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Malnutrition	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Arthralgia	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Arthritis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Back pain	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Bone pain	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.33% 3/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Myalgia	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.44% 2/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Pain in extremity	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Synovial cyst	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Abdominal wall neoplasm	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of thyroid gland	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.22% 2/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer recurrent	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.00% 0/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.11% 1/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cerebellar tumour	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	0.22% 1/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	0.00% 0/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.

Other adverse events

Measure	Placebo n=450 participants at risk Patients to receive matching placebo soft gelatine capsule identical to those containing Nintedanib, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.	Nintedanib n=902 participants at risk Patients to receive Nintedanib 200 milligram (mg) soft gelatine capsule, taken orally twice daily, except the day of chemotherapy (carboplatin and paclitaxel) infusion, every 21 days for six courses.
Blood and lymphatic system disorders Anaemia	28.7% 129/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	35.1% 317/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Leukopenia	17.3% 78/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	18.3% 165/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Neutropenia	45.1% 203/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	46.5% 419/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Blood and lymphatic system disorders Thrombocytopenia	19.3% 87/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	33.4% 301/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal distension	4.4% 20/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.1% 55/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal pain	24.7% 111/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	31.2% 281/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Abdominal pain upper	12.9% 58/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	13.9% 125/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Constipation	33.6% 151/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	28.2% 254/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Diarrhoea	25.3% 114/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	76.7% 692/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Dyspepsia	5.3% 24/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.5% 77/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Flatulence	2.0% 9/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.9% 53/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Nausea	51.3% 231/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	64.6% 583/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Stomatitis	5.3% 24/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.7% 51/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Gastrointestinal disorders Vomiting	26.4% 119/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	43.3% 391/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Asthenia	14.4% 65/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	18.1% 163/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Fatigue	44.7% 201/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	43.0% 388/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Mucosal inflammation	6.7% 30/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.9% 62/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Oedema peripheral	10.4% 47/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.3% 48/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Pain	6.0% 27/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	3.9% 35/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
General disorders Pyrexia	10.2% 46/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	7.1% 64/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Drug hypersensitivity	4.7% 21/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.4% 58/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Immune system disorders Hypersensitivity	7.1% 32/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.9% 53/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Cystitis	3.8% 17/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	7.3% 66/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Nasopharyngitis	8.0% 36/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.1% 73/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Infections and infestations Urinary tract infection	11.1% 50/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	14.5% 131/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Alanine aminotransferase increased	10.9% 49/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	28.7% 259/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Aspartate aminotransferase increased	9.1% 41/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	24.3% 219/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Blood alkaline phosphatase increased	3.6% 16/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.2% 74/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Haemoglobin decreased	5.3% 24/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.2% 56/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Neutrophil count decreased	5.1% 23/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.2% 74/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Investigations Platelet count decreased	3.8% 17/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	7.0% 63/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Decreased appetite	14.0% 63/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	18.6% 168/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypokalaemia	5.6% 25/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	9.4% 85/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 25/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	10.2% 92/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Arthralgia	30.4% 137/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	26.8% 242/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Back pain	12.0% 54/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	9.2% 83/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Bone pain	8.7% 39/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.9% 62/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.4% 29/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.2% 56/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Myalgia	23.8% 107/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	22.3% 201/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Musculoskeletal and connective tissue disorders Pain in extremity	12.4% 56/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	10.5% 95/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Dizziness	8.0% 36/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.5% 77/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Dysgeusia	8.2% 37/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	14.0% 126/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Headache	11.8% 53/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	15.5% 140/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Neuropathy peripheral	18.9% 85/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	19.1% 172/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Paraesthesia	14.2% 64/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	11.1% 100/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Peripheral sensory neuropathy	25.3% 114/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	23.7% 214/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Nervous system disorders Polyneuropathy	5.6% 25/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.5% 50/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Anxiety	6.0% 27/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	4.0% 36/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Depression	7.1% 32/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	5.7% 51/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Psychiatric disorders Insomnia	12.7% 57/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	11.6% 105/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Cough	7.6% 34/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	6.3% 57/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.2% 55/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	12.1% 109/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.8% 17/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.0% 72/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Alopecia	61.8% 278/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	57.5% 519/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Pruritus	7.1% 32/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	4.9% 44/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Skin and subcutaneous tissue disorders Rash	11.1% 50/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	10.5% 95/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Hot flush	10.0% 45/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	8.1% 73/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.
Vascular disorders Hypertension	5.1% 23/450 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.	13.2% 119/902 • First drug administration until data cut-off 26September16, up to 62 months Adverse Events were reported for the treated patients.

Additional Information

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