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Clinical Trial Results:
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)

Summary
EudraCT number	2006-001489-17
Trial protocol	AT ES GB BE DK IT IE HU FI SI PL GR
Global end of trial date	30 Jan 2025

Results information
Results version number	v1(current)
This version publication date	25 Apr 2026
First version publication date	25 Apr 2026
Other versions
Summary report(s)	HR-NBL1_SIOPEN_Public Lay Summary

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

SIOPENRNET003

ISRCTN number

US NCT number

NCT01704716

WHO universal trial number (UTN)

Other trial identifiers

HR-NBL1 (SIOPEN): HR-NBL1

Sponsor organisation name

St. Anna Kinderkrebsforschung

Sponsor organisation address

Zimmermannplatz 10, Vienna, Austria, 1090

Public contact

Ruth Ladenstein, St. Anna Kinderkrebsforschung, +43 1404704750, ruth.ladenstein@ccri.at

Scientific contact

Ruth Ladenstein, St. Anna Kinderkrebsforschung, +43 1404704750, ruth.ladenstein@ccri.at

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

15 Sep 2025

Is this the analysis of the primary completion data?

Yes

Primary completion date

30 Jan 2025

Global end of trial reached?

Yes

Global end of trial date

30 Jan 2025

Was the trial ended prematurely?

Main objective of the trial

1) R0 randomisation (2002-2005) found significantly improved treatment tolerance with prophylactic use of G-CSF during Rapid COJEC Induction: new standard of care. 2) R1 rand. (2002-2010) found signif. superiority for MAT with busulfan and melphalan (BuMel) over MAT with carboplatin, etoposide and melphalan (CEM). BuMel: new standard MAT. 3) R2 rand. comparing short-term infusion (STI) ch14.18/CHO vs. STI ch14.18/CHO + scIL2 (2006-2013) found subst. higher toxicity profile in arm with scIL2, but no survival benefit (neither EFS, nor OS). 4) R3 rand. compared Rapid COJEC vs. the modified N7 regimen (2011-2017): no outcome differ. (neither EFS nor OS) detected but more favourable toxic. profile: Rapid COJEC confirmed standard Induction regimen. 5) R4 rand. altered the duration of inf. time to 10 days ctn LTI ch14.18/CHO (same total dose) vs. LTI ch14.18/CHO + scIL2; (2014-2018): no dif. in EFS or OS, but more favourable tox. prof. without scIL2: new immunother. standard maintenance.

Protection of trial subjects

Detailed in the Study Protocol under: B. General Principles, page 252-253: 9. It is the duty of physicians who are involved in medical research to protect the life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects. The responsibility for the protection of research subjects must always rest with the physician or other health care professionals and never with the research subjects, even though they have given consent. 10. Physicians must consider the ethical, legal and regulatory norms and standards for research involving human subjects in their own countries as well as applicable international norms and standards. No national or international ethical, legal or regulatory requirement should reduce or eliminate any of the protections for research subjects set forth in this Declaration. All vulnerable groups and individuals should receive specifically considered protection.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Mar 2002

Long term follow-up planned

Yes

Long term follow-up rationale

Safety, Efficacy, Scientific research

Long term follow-up duration

3 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 27

Country: Number of subjects enrolled

Austria: 135

Country: Number of subjects enrolled

Belgium: 128

Country: Number of subjects enrolled

Czechia: 67

Country: Number of subjects enrolled

Denmark: 40

Country: Number of subjects enrolled

Finland: 20

Country: Number of subjects enrolled

France: 701

Country: Number of subjects enrolled

Greece: 74

Country: Number of subjects enrolled

Hong Kong: 29

Country: Number of subjects enrolled

Hungary: 29

Country: Number of subjects enrolled

Ireland: 30

Country: Number of subjects enrolled

Israel: 198

Country: Number of subjects enrolled

Italy: 636

Country: Number of subjects enrolled

New Zealand: 1

Country: Number of subjects enrolled

Norway: 53

Country: Number of subjects enrolled

Poland: 170

Country: Number of subjects enrolled

Portugal: 17

Country: Number of subjects enrolled

Slovakia: 29

Country: Number of subjects enrolled

Slovenia: 12

Country: Number of subjects enrolled

Spain: 380

Country: Number of subjects enrolled

Sweden: 78

Country: Number of subjects enrolled

Switzerland: 45

Country: Number of subjects enrolled

United Kingdom: 678

Worldwide total number of subjects

3577

EEA total number of subjects

2599

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

993

Children (2-11 years)

2488

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

FPFV (first patient in): 23-Apr-2002 LPFV (last patient in): 14-Jun-2023 LPLV (last patient out): 30-Jan-2025 End of global recruitment: 31-Jul-2023 Total number of patients recruited: 3569 Number of recruiting countries: 23 Number of sites with recruited patients: 188

Screening details

Pre-registration is only possible if the eligibility criteria are met. Registration will be final once the disease description at diagnosis including MYCN results is complete.

Period 1 title

Total Study Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

BUMEL (Cohort R1)

Arm description

BUMEL - busulfan and melphalan

Arm type

Experimental

Investigational medicinal product name

Busulfan

Investigational medicinal product code

ATC code: L01AB01

Other name

Busilvex, Busulphan, Myleran

Pharmaceutical forms

Solution for infusion, Tablet

Routes of administration

Intravenous use, Oral use

Dosage and administration details

The BuMel MAT regimen consists of oral administration of busulphan and the short i.v. infusion of melphalan. In July 2007 (Amendment 3) oral busulfan was changed to i.v. busulfan (Busilvex). Oral busulfan is given at 37.5 mg/m²/dose every 6 hours for a total of 16 doses over 4 consecutive days (total 600 mg/m²). Intravenous administration of busulfan (Busilvex) consists of a two-hour infusion every 6 hours over 4 (or 5) consecutive days through a central venous catheter only with dosage according to BW: < 9 kg: 1.0 mg/kg 9 kg to < 16 kg: 1.2 mg/kg 16 kg to 23 kg: 1.1 mg/kg >23 kg to 34 kg: 0.95 mg/kg >34 kg: 0.8 mg/kg

Investigational medicinal product name

Melphalan

Investigational medicinal product code

HS Code: 3004.90

Other name

Alkeran

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Injection

Dosage and administration details

In case of body weight below 12 kg the melphalan dose calculation is recommended to be dosed by kg/BW, i.e. 4 mg/kg. For infants with a weight ≤ 5 kg, a further 1/3 reduction is advised. Short i.v. infusion.

CEM (Cohort R1)

Arm description

CEM - MAT carboplatin, etoposide, and melphalan

Arm type

Active comparator

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

ATC Code: LO1X A02

Other name

Paraplatin

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]

Investigational medicinal product name

Etoposide

Investigational medicinal product code

ATC code: L01CB01

Other name

VP16

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

350 mg/m²/course

Investigational medicinal product name

Melphalan

Investigational medicinal product code

ATC code: L01AA03

Other name

Alkeran

Pharmaceutical forms

Powder for injection

Routes of administration

Intravenous use

Dosage and administration details

210 mg/m²/course

STI ch14.18/CHO (Cohort R2)

Arm description

anti-GD2 antibody ch14.18/CHO (Dinutuximab beta)

Arm type

Active comparator

Investigational medicinal product name

ch14.18/CHO antibody

Investigational medicinal product code

Other name

Chimeric 14.18 anti-GD2 monoclonal antibody, Dinutuximab beta, Qarziba

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

ch14.18/CHO is given at a dose of 20 mg/m²/day over five days every four weeks for five courses.

STI ch14.18/CHO + scIL-2 (Cohort R2)

Arm description

anti-GD2 antibody ch14.18/CHO (Dinutuximab beta) and subcutaneous IL-2

Arm type

Experimental

Investigational medicinal product name

ch14.18/CHO antibody

Investigational medicinal product code

Other name

Chimeric 14.18 anti-GD2 monoclonal antibody, Dinutuximab beta, Qarziba

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

ch14.18/CHO is given at a dose of 20 mg/m²/day over five days every four weeks for five courses.

Investigational medicinal product name

Aldesleukin

Investigational medicinal product code

ATC code: L03AC01

Other name

Interleukin 2, IL-2, IL2, Proleukin

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use, Subcutaneous use

Dosage and administration details

3-18 × 10⁶ IU/m²/day continuous i.v. infusion for 4–5 days.

COJEC (Cohort R3)

Arm description

Rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C])

Arm type

Active comparator

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

ATC Code: L01XA01

Other name

CDDP

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

80 mg/m²/24 hours. In case of body weight below 12 kg the dose of 2.666 mg/kg. For infants with a weight < or equal to 5 kg, a further 1/3 reduction is advised.

Investigational medicinal product name

Vincristine

Investigational medicinal product code

ATC code: L01CA02

Other name

VCR

Pharmaceutical forms

Solution for injection

Routes of administration

Infusion , Intravenous use

Dosage and administration details

1.5 mg/m² (maximum dose 2 mg) as a single i.v. bolus. In case of body weight below 12 kg the dose of 0.05 mg/kg.

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

ATC Code: LO1X A02

Other name

CBDCA, Paraplatin

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25].

Investigational medicinal product name

Etoposide

Investigational medicinal product code

ATC code: L01CB01

Other name

VP16

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

350 mg/m²/course

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

ATC code: L01AA01

Other name

CYC, Endoxan

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

2.1 g/m²/course

N7 (Cohort R3)

Arm description

Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5)

Arm type

Experimental

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

ATC Code: L01XA01

Other name

CDDP

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

80 mg/m²/24 hours. In case of body weight below 12 kg the dose of 2.666 mg/kg. For infants with a weight < or equal to 5 kg, a further 1/3 reduction is advised.

Investigational medicinal product name

Vincristine

Investigational medicinal product code

ATC code: L01CA02

Other name

VCR

Pharmaceutical forms

Solution for injection

Routes of administration

Infusion , Intravenous use

Dosage and administration details

1.5 mg/m² (maximum dose 2 mg) as a single i.v. bolus. In case of body weight below 12 kg the dose of 0.05 mg/kg.

Investigational medicinal product name

Doxorubicin

Investigational medicinal product code

ATC code: L01DB01

Other name

DOXO, Adriamycin

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use, Intravesical use

Dosage and administration details

22.5 mg/m²/day in a 48-hour continuous infusion. Infants and children with a body weight below 12 kg should be dosed according to their weight in kg instead of their body surface area (m²) according to the known formula of 30 kg = 1 m². Doxorubicin: 0.75 mg/kg/day.

Investigational medicinal product name

Etoposide

Investigational medicinal product code

ATC code: L01CB01

Other name

VP16

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

350 mg/m²/course.

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

ATC code: L01AA01

Other name

CYC, Endoxan

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

2.1 g/m²/course.

Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Arm description

Cont. infusion of ch14.18/CHO and oral 13-cis-retinoic acid (RA)

Arm type

Active comparator

Investigational medicinal product name

ch14.18/CHO antibody

Investigational medicinal product code

Other name

Chimeric 14.18 anti-GD2 monoclonal antibody, Dinutuximab beta, Qarziba

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

ch14.18/CHO is given at a dose of 20 mg/m²/day over five days every four weeks for five courses.

Investigational medicinal product name

Isotretinoin

Investigational medicinal product code

ATC code: D10BA01

Other name

13-cis-retinoic acid, 13-cis-RA, Roaccutan

Pharmaceutical forms

Capsule, soft

Routes of administration

Oral use

Dosage and administration details

Patients will receive isotretinoin (13-cis-RA) 160 mg/m²/day divided into two equal doses given orally twice a day for 14 days after the completion of the ch14.18/CHO infusion. The starting day is dependent on the duration of ch14.18/CHO infusion and may be either day 19, 23, 24 or 30.

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)

Arm description

Cont. infusion of ch14.18/CHO + scIL-2

Arm type

Experimental

Investigational medicinal product name

ch14.18/CHO antibody

Investigational medicinal product code

Other name

Chimeric 14.18 anti-GD2 monoclonal antibody, Dinutuximab beta, Qarziba

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

ch14.18/CHO is given at a dose of 20 mg/m²/day over five days every four weeks for five courses.

Investigational medicinal product name

Aldesleukin

Investigational medicinal product code

ATC code: L03AC01

Other name

Interleukin 2, IL-2, IL2, Proleukin

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous use, Subcutaneous use

Dosage and administration details

3-18 × 10⁶ IU/m²/day continuous i.v. infusion for 4–5 days.

PPGCSF (Cohort R0)

Arm description

Primary prophylactic (PP) use of granulocyte colony-stimulating factor (G-CSF) during COJEC

Arm type

Experimental

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

ATC Code: L01XA01

Other name

CDDP

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

80 mg/m²/24 hours. In case of body weight below 12 kg the dose of 2.666 mg/kg. For infants with a weight < or equal to 5 kg, a further 1/3 reduction is advised.

Investigational medicinal product name

Vincristine

Investigational medicinal product code

ATC code: L01CA02

Other name

VCR

Pharmaceutical forms

Solution for injection

Routes of administration

Infusion , Intravenous use

Dosage and administration details

1.5 mg/m² (maximum dose 2 mg) as a single i.v. bolus. In case of body weight below 12 kg the dose of 0.05 mg/kg.

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

ATC Code: LO1X A02

Other name

CBDCA, Paraplatin

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]

Investigational medicinal product name

Etoposide

Investigational medicinal product code

ATC code: L01CB01

Other name

VP16

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

350 mg/m²/course

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

ATC code: L01AA01

Other name

CYC, Endoxan

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

2.1 g/m²/course

Investigational medicinal product name

G-CSF

Investigational medicinal product code

ATC code: L03AA

Other name

Filgrastim, Nivestim, Filgrastim HEXAL, NEUPOGEN, NEULASTA, ACCOFIL

Pharmaceutical forms

Concentrate for solution for injection, Solution for infusion, Solution for injection

Routes of administration

Intravenous use, Subcutaneous use

Dosage and administration details

A single daily subcutaneous injection of 10 microgram/kg/day for 5 days, beginning at least 24 hours after the last chemotherapy dose.

STGCSF (Cohort R0)

Arm description

Control Arm with symptom-triggered granulocyte colony-stimulating factor (ST G-CSF) during COJEC

Arm type

Active comparator

Investigational medicinal product name

Cisplatin

Investigational medicinal product code

ATC Code: L01XA01

Other name

CDDP

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

80 mg/m²/24 hours. In case of body weight below 12 kg the dose of 2.666 mg/kg. For infants with a weight < or equal to 5 kg, a further 1/3 reduction is advised.

Investigational medicinal product name

Vincristine

Investigational medicinal product code

ATC code: L01CA02

Other name

VCR

Pharmaceutical forms

Solution for injection

Routes of administration

Infusion , Intravenous use

Dosage and administration details

1.5 mg/m² (maximum dose 2 mg) as a single i.v. bolus. In case of body weight below 12 kg the dose of 0.05 mg/kg.

Investigational medicinal product name

Carboplatin

Investigational medicinal product code

ATC Code: LO1X A02

Other name

CBDCA, Paraplatin

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Dose (mg) = target AUC (mg/ml x min) x [GFR ml/min + 25]

Investigational medicinal product name

Etoposide

Investigational medicinal product code

ATC code: L01CB01

Other name

VP16

Pharmaceutical forms

Concentrate for solution for infusion

Routes of administration

Infusion , Intravenous use

Dosage and administration details

350 mg/m²/course.

Investigational medicinal product name

Cyclophosphamide

Investigational medicinal product code

ATC code: L01AA01

Other name

CYC, Endoxan

Pharmaceutical forms

Coated tablet

Routes of administration

Oral use

Dosage and administration details

2.1 g/m²/course

Observational Cohort

Arm description

Non-randomised Standard of Care (observational cohort)

Arm type

Standard of care

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Number of subjects in period 1	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)	PPGCSF (Cohort R0)	STGCSF (Cohort R0)	Observational Cohort
Started	296	302	200	206	313	317	205	202	119	120	1710
Completed	292	278	160	118	288	292	162	129	110	114	1710
Not completed	4	24	40	88	25	25	43	73	9	6	0
Adverse event, serious fatal	-	-	-	-	-	2	-	-	-	-	-
change to COJEC	-	-	-	-	-	4	-	-	-	-	-
Physician decision	-	-	-	-	-	-	1	-	-	-	-
Toxicity	-	-	-	-	6	-	-	-	3	1	-
stopped immunotherapy	-	-	21	57	-	-	-	-	-	-	-
poor response	-	-	-	-	-	-	-	-	2	2	-
Adverse event, non-fatal	-	-	-	-	-	7	8	-	-	-	-
did not received dinutuximab beta	-	-	12	11	-	-	-	-	-	-	-
GD2 or IL2 not given	-	-	-	-	-	-	-	13	-	-	-
change to other treatment	-	-	-	-	6	-	-	-	-	-	-
disease progression	-	5	-	-	-	3	19	-	-	-	-
change to N 7	-	-	-	-	1	-	-	-	-	-	-
not received N7	-	-	-	-	-	4	-	-	-	-	-
Toxicity -death	-	-	-	-	-	-	-	-	1	-	-
GD2 not given	-	-	-	-	-	-	4	-	-	-	-
interrupted immunotherapy	-	-	3	13	-	-	-	-	-	-	-
parental decision	-	-	-	-	-	-	-	-	-	1	-
received busulfan and melphalan	-	18	-	-	-	-	-	-	-	-	-
Death- progression of disease	-	-	-	-	-	-	-	-	3	-	-
not received COJEC	-	-	-	-	2	-	-	-	-	-	-
received carboplatin, etoposide and melphalan	3	-	-	-	-	-	-	-	-	-	-
did not received IL2	-	-	-	3	-	-	-	-	-	-	-
Complications	-	-	-	-	-	-	2	-	-	2	-
incomplete therapy data	-	-	4	4	9	-	8	16	-	-	-
unknown	-	-	-	-	-	3	1	-	-	-	-
Decision to surgery	-	-	-	-	-	2	-	-	-	-	-
disease progression before	1	-	-	-	-	-	-	-	-	-	-
stopped or interrupted therapy	-	-	-	-	-	-	-	44	-	-	-
Lost to follow-up	-	1	-	-	-	-	-	-	-	-	-
Lack of efficacy	-	-	-	-	1	-	-	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

Total Study Period

Reporting group description

HR-NBL1 Study Period: 02.02.2002 - 30.1.2025

Reporting group values	Total Study Period	Total
Number of subjects	3577	3577
Age categorical
Age categorical
Units: Subjects
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	6	6
Infants and toddlers (28 days-23 months)	993	993
Children (2-11 years)	2488	2488
Adolescents (12-17 years)	81	81
Adults (18-64 years)	9	9
From 65-84 years	0	0
85 years and over	0	0
Age continuous
Age continuous
Units: years
median (standard deviation)	2.92 ( 2.8 )	-
Gender categorical
Gender
Units: Subjects
Female	1515	1515
Male	2062	2062

End points

Top of page

Reporting group title

BUMEL (Cohort R1)

Reporting group description

BUMEL - busulfan and melphalan

Reporting group title

CEM (Cohort R1)

Reporting group description

CEM - MAT carboplatin, etoposide, and melphalan

Reporting group title

STI ch14.18/CHO (Cohort R2)

Reporting group description

anti-GD2 antibody ch14.18/CHO (Dinutuximab beta)

Reporting group title

STI ch14.18/CHO + scIL-2 (Cohort R2)

Reporting group description

anti-GD2 antibody ch14.18/CHO (Dinutuximab beta) and subcutaneous IL-2

Reporting group title

COJEC (Cohort R3)

Reporting group description

Rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C])

Reporting group title

N7 (Cohort R3)

Reporting group description

Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5)

Reporting group title

Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Reporting group description

Cont. infusion of ch14.18/CHO and oral 13-cis-retinoic acid (RA)

Reporting group title

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)

Reporting group description

Cont. infusion of ch14.18/CHO + scIL-2

Reporting group title

PPGCSF (Cohort R0)

Reporting group description

Primary prophylactic (PP) use of granulocyte colony-stimulating factor (G-CSF) during COJEC

Reporting group title

STGCSF (Cohort R0)

Reporting group description

Control Arm with symptom-triggered granulocyte colony-stimulating factor (ST G-CSF) during COJEC

Reporting group title

Observational Cohort

Reporting group description

Non-randomised Standard of Care (observational cohort)

Primary: 3-years Event-free survival - EFS

Top of page

End point title

3-years Event-free survival - EFS ^[1]

End point description

End point type

Primary

End point timeframe

3 years

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. This endpoint EFS is designated as the primary endpoint for cohorts R1, R2, R3, R4.

End point values	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)
Number of subjects analysed	296	301 ^[2]	200	206	312 ^[3]	314 ^[4]	205	200 ^[5]
Units: Patients	296	302	200	206	313	317	205	202

Notes
[2] - No follow-up information was reported for one patient
[3] - No follow-up information was reported for one patient
[4] - No follow-up information was reported for three patients
[5] - No follow-up information was reported for two patients

EFS Comparison Cohort R1

Statistical analysis description

high-dose chemotherapy with busulfan and melphalan (BUMEL) compared with carboplatin, etoposide, and melphalan (CEM)

Comparison groups

BUMEL (Cohort R1) v CEM (Cohort R1)

Number of subjects included in analysis

597

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.001

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.713

Confidence interval

level

95%

sides

2-sided

lower limit

0.582

upper limit

0.873

EFS Comparison Cohort R2

Statistical analysis description

STI ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2 compared with dinutuximab beta alone

Comparison groups

STI ch14.18/CHO + scIL-2 (Cohort R2) v STI ch14.18/CHO (Cohort R2)

Number of subjects included in analysis

406

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.457

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.897

Confidence interval

level

95%

sides

2-sided

lower limit

0.673

upper limit

1.195

EFS Comparison Cohort R3

Statistical analysis description

difference in efficacy between MSKCC-N5 and rCOJEC: modified N7 vs Rapid COJEC

Comparison groups

N7 (Cohort R3) v COJEC (Cohort R3)

Number of subjects included in analysis

626

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.277

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.892

Confidence interval

level

95%

sides

2-sided

lower limit

0.727

upper limit

1.096

EFS Comparison Cohort R4

Statistical analysis description

continuous infusion of LTI ch14.18/CHO ± aldesleukin (IL-2): LTI ch14.18/CHO + scIL-2 vs LTI ch14.18/CHO

Comparison groups

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4) v Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.825

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.966

Confidence interval

level

95%

sides

2-sided

lower limit

0.707

upper limit

1.318

Secondary: 3-years Overall survival - OS

Top of page

End point title

3-years Overall survival - OS ^[6]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. This endpoint OS is designated as the primary endpoint for cohorts R1, R2, R3, R4.

End point values	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)
Number of subjects analysed	296	301 ^[7]	200	206	312 ^[8]	314 ^[9]	205	200 ^[10]
Units: Patients	296	302	200	206	313	317	205	202

Notes
[7] - No follow-up information was reported for one patient
[8] - No follow-up information was reported for one patient
[9] - No follow-up information was reported for three patients
[10] - No follow-up information was reported for two patients

OS Comparison Cohort R1

Statistical analysis description

high-dose chemotherapy with busulfan and melphalan (BUMEL) compared with carboplatin, etoposide, and melphalan (CEM)

Comparison groups

BUMEL (Cohort R1) v CEM (Cohort R1)

Number of subjects included in analysis

597

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.714

Confidence interval

level

95%

sides

2-sided

lower limit

0.579

upper limit

0.882

OS Comparison Cohort R2

Statistical analysis description

ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2 compared with dinutuximab beta alone

Comparison groups

STI ch14.18/CHO + scIL-2 (Cohort R2) v STI ch14.18/CHO (Cohort R2)

Number of subjects included in analysis

406

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.972

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.995

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.355

OS Comparison Cohort R3

Statistical analysis description

difference in efficacy between MSKCC-N5 and rCOJEC: modified N7 vs Rapid COJEC

Comparison groups

N7 (Cohort R3) v COJEC (Cohort R3)

Number of subjects included in analysis

626

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.113

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.832

Confidence interval

level

95%

sides

2-sided

lower limit

0.664

upper limit

1.044

OS Comparison Cohort R4

Statistical analysis description

continuous infusion of ch14.18/CHO + retinoic acid (RA) ± aldesleukin (IL-2): LTI ch14.18/CHO + scIL-2 vs LTI ch14.18/CHO

Comparison groups

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4) v Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.536

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.897

Confidence interval

level

95%

sides

2-sided

lower limit

0.637

upper limit

1.265

Secondary: 3-years Cumulative incidence of relapse - CIR

Top of page

End point title

3-years Cumulative incidence of relapse - CIR ^[11]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. This endpoint CIR is designated as the primary endpoint for cohorts R1, R2, R3, R4.

End point values	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)
Number of subjects analysed	296	301 ^[12]	200	206	312 ^[13]	314 ^[14]	205	200 ^[15]
Units: Patients	296	302	200	206	313	317	205	202

Notes
[12] - No follow-up information was reported for one patient
[13] - No follow-up information was reported for one patient
[14] - No follow-up information was reported for three patients
[15] - No follow-up information was reported for two patients

CIR Comparison Cohort R1

Statistical analysis description

high-dose chemotherapy with busulfan and melphalan (BUMEL) compared with carboplatin, etoposide, and melphalan (CEM)

Comparison groups

BUMEL (Cohort R1) v CEM (Cohort R1)

Number of subjects included in analysis

597

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.753

Confidence interval

level

95%

sides

2-sided

lower limit

0.61

upper limit

0.93

CIR Comparison Cohort R2

Statistical analysis description

STI ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2 compared with dinutuximab beta alone

Comparison groups

STI ch14.18/CHO (Cohort R2) v STI ch14.18/CHO + scIL-2 (Cohort R2)

Number of subjects included in analysis

406

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.65

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.934

Confidence interval

level

95%

sides

2-sided

lower limit

0.695

upper limit

1.254

CIR Comparison Cohort R3

Statistical analysis description

difference in efficacy between MSKCC-N5 and rCOJEC: modified N7 vs Rapid COJEC

Comparison groups

N7 (Cohort R3) v COJEC (Cohort R3)

Number of subjects included in analysis

626

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.206

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.867

Confidence interval

level

95%

sides

2-sided

lower limit

0.694

upper limit

1.082

CIR Comparison Cohort R4

Statistical analysis description

Retinoic acid (RA) + continuous infusion of ch14.18/CHO ± aldesleukin (IL-2): RA + LTI ch14.18/CHO + scIL-2 vs LTI ch14.18/CHO

Comparison groups

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4) v Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.426

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.875

Confidence interval

level

95%

sides

2-sided

lower limit

0.629

upper limit

1.216

Secondary: 3-years Non-relapse mortality - NRM

Top of page

End point title

3-years Non-relapse mortality - NRM ^[16]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. This endpoint NRM is designated as the primary endpoint for cohorts R1, R2, R3, R4.

End point values	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)
Number of subjects analysed	296	301 ^[17]	200	206	312 ^[18]	314 ^[19]	205	200 ^[20]
Units: Patients	296	302	200	206	313	317	205	202

Notes
[17] - No follow-up information was reported for one patient
[18] - No follow-up information was reported for one patient
[19] - No follow-up information was reported for three patients
[20] - No follow-up information was reported for two patients

NRM Comparison Cohort R1

Statistical analysis description

high-dose chemotherapy with busulfan and melphalan (BUMEL) compared with carboplatin, etoposide, and melphalan (CEM)

Comparison groups

BUMEL (Cohort R1) v CEM (Cohort R1)

Number of subjects included in analysis

597

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.045

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.409

Confidence interval

level

95%

sides

2-sided

lower limit

0.17

upper limit

0.982

NRM Comparison Cohort R2

Statistical analysis description

STI ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2 compared with dinutuximab beta alone

Comparison groups

STI ch14.18/CHO + scIL-2 (Cohort R2) v STI ch14.18/CHO (Cohort R2)

Number of subjects included in analysis

406

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.456

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.139

upper limit

2.423

NRM Comparison Cohort R3

Statistical analysis description

difference in efficacy between MSKCC-N5 and rCOJEC: modified N7 vs Rapid COJEC

Comparison groups

N7 (Cohort R3) v COJEC (Cohort R3)

Number of subjects included in analysis

626

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.408

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

1.279

Confidence interval

level

95%

sides

2-sided

lower limit

0.714

upper limit

2.288

NRM Comparison Cohort R4

Statistical analysis description

Retinoic acid (RA) + continuous infusion of ch14.18/CHO ± aldesleukin (IL-2): RA + LTI ch14.18/CHO + scIL-2 vs LTI ch14.18/CHO

Comparison groups

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4) v Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.133

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

2.771

Confidence interval

level

95%

sides

2-sided

lower limit

0.734

upper limit

10.462

Secondary: 3-years Cumulative incidence of secondary malignancies

Top of page

End point title

3-years Cumulative incidence of secondary malignancies ^[21]

End point description

End point type

Secondary

End point timeframe

3 years

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. This endpoint is designated as the primary endpoint for cohorts R1, R2, R3, R4.

End point values	BUMEL (Cohort R1)	CEM (Cohort R1)	STI ch14.18/CHO (Cohort R2)	STI ch14.18/CHO + scIL-2 (Cohort R2)	COJEC (Cohort R3)	N7 (Cohort R3)	Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)	Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4)
Number of subjects analysed	296	301 ^[22]	200	206	312 ^[23]	314 ^[24]	205	200 ^[25]
Units: Patients	296	302	200	206	313	317	205	202

Notes
[22] - No follow-up information was reported for one patient
[23] - No follow-up information was reported for one patient
[24] - No follow-up information was reported for three patients
[25] - No follow-up information was reported for two patients

Comparison of CI of sec. malignancies Cohort R1

Statistical analysis description

high-dose chemotherapy with busulfan and melphalan (BUMEL) compared with carboplatin, etoposide, and melphalan (CEM)

Comparison groups

BUMEL (Cohort R1) v CEM (Cohort R1)

Number of subjects included in analysis

597

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.049

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

8.084

Confidence interval

level

95%

sides

2-sided

lower limit

1.011

upper limit

64.645

Comparison of CI of sec. malignancies Cohort R2

Statistical analysis description

ch14.18/CHO (dinutuximab beta) and subcutaneous IL-2 compared with dinutuximab beta alone

Comparison groups

STI ch14.18/CHO + scIL-2 (Cohort R2) v STI ch14.18/CHO (Cohort R2)

Number of subjects included in analysis

406

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.563

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.495

Confidence interval

level

95%

sides

2-sided

lower limit

0.046

upper limit

5.366

Comparison of CI of sec. malignancies Cohort R3

Statistical analysis description

difference in efficacy between MSKCC-N5 and rCOJEC: modified N7 vs Rapid COJEC

Comparison groups

N7 (Cohort R3) v COJEC (Cohort R3)

Number of subjects included in analysis

626

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.255

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

0.385

Confidence interval

level

95%

sides

2-sided

lower limit

0.074

upper limit

1.991

Comparison of CI of sec. malignancies Cohort R4

Statistical analysis description

continuous infusion of ch14.18/CHO + retinoic acid (RA) ± aldesleukin (scIL-2): LTI ch14.18/CHO + RA + scIL-2 vs RA + LTI ch18.14/CHO

Comparison groups

Retinoic acid (RA) + LTI ch14.18/CHO + scIL-2 (Cohort R4) v Retinoic acid (RA) + LTI ch14.18/CHO (Cohort R4)

Number of subjects included in analysis

405

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.682

Method

Wald test

Parameter type

Hazard ratio (HR)

Point estimate

1.366

Confidence interval

level

95%

sides

2-sided

lower limit

0.307

upper limit

6.081

Other pre-specified: Number of febrile episodes per course

Top of page

End point title

Number of febrile episodes per course ^[26]

End point description

This endpoint is designated as the primary endpoint for cohort R0.

End point type

Other pre-specified

End point timeframe

during COJEC

Notes
[26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study had a total of 5 randomizations. Endpoints were predefined on a cohort-specific basis in accordance with the scientific objectives of each cohort. As a result, not all endpoints are applicable to every study arm. "Number of febrile episodes per course" is not available for all treatment arms. This endpoint is designated as the primary endpoint for cohort R0.

End point values	PPGCSF (Cohort R0)	STGCSF (Cohort R0)
Number of subjects analysed	119	119
Units: Episodes/Cycle
arithmetic mean (standard deviation)	2.3 ( 1.9 )	3.1 ( 1.9 )

Mean Difference Between Groups

Comparison groups

PPGCSF (Cohort R0) v STGCSF (Cohort R0)

Number of subjects included in analysis

238

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

t-test, 2-sided

Parameter type

Mean difference (final values)

Point estimate

0.763

Confidence interval

level

90%

sides

2-sided

lower limit

0.284

upper limit

1.242

Adverse events

Top of page

Timeframe for reporting adverse events

Defined in the Study Protocol: 27 APPENDIX: Guidelines for Reporting Toxicity/Serious Adverse Events.

Adverse event reporting additional description

The following events are exempt from reporting via the SAE CRF in the database: • Relapse • Signs and symptoms of disease progression • Death from disease progression

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

IND (randomised COJEC)

Reporting group description

Induction - randomised COJEC

Reporting group title

IND (randomised N7)

Reporting group description

Induction - randomised N7

Reporting group title

IND (not randomised)

Reporting group description

Induction - not randomised

Reporting group title

TVD.

Reporting group description

TVD Topotecan, Vincristine, Doxorubicin

Reporting group title

SURGERY

Reporting group description

Surgery

Reporting group title

MAT (randomised BUMEL)

Reporting group description

Myeloablative therapy MAT - randomised BuMel - Busulfan (Busilvex), Melphalan

Reporting group title

MAT (randomised CEM)

Reporting group description

Myeloablative therapy MAT - randomised CEM - Carboplatin, Etoposide, Melphalan

Reporting group title

MAT (not randomised)

Reporting group description

Myeloablative therapy MAT - not randomised

Reporting group title

RADIOTHERAPY

Reporting group description

Radiotherapy

Reporting group title

MRD (R2 randomised GD2 only)

Reporting group description

Minimal residual disease MRD - R2 randomised GD2 only

Reporting group title

MRD (R2 randomised GD2 + IL-2)

Reporting group description

Minimal residual disease MRD - R2 randomised GD2 + IL-2

Reporting group title

MRD (R4 randomised GD2 only)

Reporting group description

Minimal residual disease MRD - R4 randomised GD2 only

Reporting group title

MRD (R4 randomised GD2 + IL-2)

Reporting group description

Minimal residual disease MRD - R4 randomised GD2 + IL-2

Reporting group title

MRD (not randomised)

Reporting group description

Minimal residual disease MRD - not randomised

Reporting group title

Other occ. phase, missing

Reporting group description

Other occurrence phase, missing

Notes
[1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
Justification: Non-serious Adverse Events were not MedDRA coded but encountered toxicities were captured according to CTS coding in the clinical trial database.

IND (randomised COJEC)

IND (randomised N7)

IND (not randomised)

TVD.

SURGERY

MAT (randomised BUMEL)

MAT (randomised CEM)

MAT (not randomised)

RADIOTHERAPY

MRD (R2 randomised GD2 only)

MRD (R2 randomised GD2 + IL-2)

MRD (R4 randomised GD2 only)

MRD (R4 randomised GD2 + IL-2)

MRD (not randomised)

Other occ. phase, missing

Total subjects affected by serious adverse events

subjects affected / exposed

54 / 313 (17.25%)

103 / 316 (32.59%)

471 / 2830 (16.64%)

66 / 1308 (5.05%)

104 / 2700 (3.85%)

58 / 296 (19.59%)

94 / 301 (31.23%)

310 / 1804 (17.18%)

42 / 2092 (2.01%)

82 / 200 (41.00%)

169 / 206 (82.04%)

57 / 205 (27.80%)

68 / 202 (33.66%)

104 / 975 (10.67%)

145 / 3566 (4.07%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Acute lymphocytic leukaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute myeloid leukaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

5 / 3566 (0.14%)

occurrences causally related to treatment / all

0 / 0

3 / 5

deaths causally related to treatment / all

0 / 0

Leukaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Medulloblastoma

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Myelodysplastic syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

3 / 3566 (0.08%)

occurrences causally related to treatment / all

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Secondary malignancy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Squamous cell carcinoma

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tumour haemorrhage

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour lysis syndrome

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Air embolism

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aortic thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Brachiocephalic vein thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Capillary leak syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

11 / 206 (5.34%)

4 / 205 (1.95%)

6 / 202 (2.97%)

3 / 975 (0.31%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

4 / 11

1 / 4

6 / 7

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Circulatory collapse

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cyanosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Distributive shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemorrhage

subjects affected / exposed

5 / 313 (1.60%)

2 / 316 (0.63%)

13 / 2830 (0.46%)

1 / 1308 (0.08%)

6 / 2700 (0.22%)

1 / 296 (0.34%)

2 / 301 (0.66%)

3 / 1804 (0.17%)

1 / 2092 (0.05%)

1 / 200 (0.50%)

3 / 206 (1.46%)

0 / 205 (0.00%)

0 / 202 (0.00%)

2 / 975 (0.21%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 5

0 / 2

2 / 14

0 / 1

0 / 6

1 / 1

0 / 2

0 / 3

0 / 1

0 / 3

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

Haemorrhage intracranial

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypertensive crisis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

2 / 301 (0.66%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

1 / 205 (0.49%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypovolaemic shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Lymphatic fistula

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Lymphorrhoea

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant hypertension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Shock haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vena cava thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

Adrenalectomy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bladder catheterisation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Duodenostomy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Haemodialysis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mechanical ventilation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nephrectomy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Resuscitation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombectomy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Administration site extravasation

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Administration site swelling

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Asthenia

subjects affected / exposed

1 / 313 (0.32%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

2 / 1308 (0.15%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Drug withdrawal syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Extravasation

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gait disturbance

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mucosal ulceration

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

1 / 1308 (0.08%)

2 / 2700 (0.07%)

1 / 296 (0.34%)

4 / 301 (1.33%)

3 / 1804 (0.17%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

8 / 3566 (0.22%)

occurrences causally related to treatment / all

0 / 0

1 / 4

0 / 1

0 / 2

0 / 1

0 / 5

0 / 3

0 / 0

0 / 1

0 / 0

0 / 8

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

Oedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

2 / 975 (0.21%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumatosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Anaphylactic reaction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

2 / 206 (0.97%)

1 / 205 (0.49%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

1 / 2

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anaphylactic shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

2 / 200 (1.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchospasm

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chronic graft versus host disease

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Drug hypersensitivity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

4 / 206 (1.94%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 3

0 / 0

2 / 6

0 / 0

deaths causally related to treatment / all

0 / 0

Engraftment syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Graft versus host disease

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypersensitivity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

8 / 206 (3.88%)

0 / 205 (0.00%)

1 / 202 (0.50%)

2 / 975 (0.21%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

5 / 10

0 / 0

1 / 1

1 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Serum sickness-like reaction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acinetobacter sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

1 / 202 (0.50%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Alpha haemolytic streptococcal infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ophthalmic herpes zoster

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute pulmonary oedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute respiratory distress syndrome

subjects affected / exposed

1 / 313 (0.32%)

1 / 316 (0.32%)

2 / 2830 (0.07%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

2 / 301 (0.66%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

4 / 3566 (0.11%)

occurrences causally related to treatment / all

1 / 1

0 / 1

0 / 2

0 / 1

0 / 0

0 / 1

0 / 2

3 / 3

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

deaths causally related to treatment / all

1 / 1

0 / 0

Acute respiratory failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Apnoea

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchial secretion retention

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchospasm

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

2 / 200 (1.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

3 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Chylothorax

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cough

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diffuse alveolar damage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Epistaxis

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemothorax

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Interstitial lung disease

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

1 / 2092 (0.05%)

2 / 200 (1.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

1 / 1

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Laryngospasm

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

2 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Lung consolidation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

3 / 1804 (0.17%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung infiltration

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Obliterative bronchiolitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Organising pneumonia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

3 / 1804 (0.17%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

1 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pneumothorax

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Pulmonary alveolar haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary arterial hypertension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Pulmonary congestion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary fibrosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

2 / 2092 (0.10%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Pulmonary haemorrhage

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

1 / 1

0 / 0

0 / 1

0 / 0

Pulmonary hypertension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

6 / 1804 (0.33%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 7

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary oedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Pulmonary toxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary veno-occlusive disease

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

5 / 1804 (0.28%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

4 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 2

0 / 0

Respiratory distress

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

2 / 296 (0.68%)

1 / 301 (0.33%)

7 / 1804 (0.39%)

0 / 2092 (0.00%)

4 / 200 (2.00%)

5 / 206 (2.43%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 5

0 / 0

0 / 2

1 / 2

0 / 1

3 / 7

0 / 0

0 / 4

2 / 5

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Respiratory failure

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

1 / 296 (0.34%)

1 / 301 (0.33%)

8 / 1804 (0.44%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

2 / 205 (0.98%)

2 / 202 (0.99%)

0 / 975 (0.00%)

4 / 3566 (0.11%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

4 / 9

0 / 0

2 / 2

0 / 0

0 / 4

deaths causally related to treatment / all

0 / 0

Tracheal disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Venoocclusive liver disease

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Affective disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Agitation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anxiety

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Depressed mood

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hallucination

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nightmare

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

Device dislocation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood creatine increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood potassium increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood pressure systolic decreased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eosinophil count increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Glomerular filtration rate decreased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutrophil count decreased

subjects affected / exposed

1 / 313 (0.32%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oxygen saturation decreased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transaminases increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vasoactive intestinal polypeptide increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Weight increased

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Accidental overdose

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Aortic injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

5 / 2700 (0.19%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

Arrhythmia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood stem cell transplant failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Brain herniation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardio-respiratory failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diaphragmatic injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Drug dose omission by device

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Engraft failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fall

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Femur fracture

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

2 / 202 (0.99%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal procedural complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal stoma complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Graft complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Horner's syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Incorrect dosage administered

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Lymphatic duct injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Overdose

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngeal injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

1 / 1

deaths causally related to treatment / all

0 / 0

Post procedural fistula

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Post procedural myocardial infarction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Postoperative adhesion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Postoperative thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Procedural complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Procedural haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

3 / 2700 (0.11%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Procedural hypotension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Procedural shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal procedural complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Retroperitoneal haematoma

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Transfusion reaction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transfusion-related acute lung injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transplantation complication

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vascular pseudoaneurysm

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vena cava injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wrong product administered

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Cytogenetic abnormality

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Gastroschisis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrioventricular block

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bradycardia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 313 (0.00%)

2 / 316 (0.63%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

0 / 301 (0.00%)

3 / 1804 (0.17%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 3

0 / 0

0 / 2

0 / 0

0 / 3

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure acute

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure congestive

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac insuffiency

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardio-respiratory arrest

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiogenic shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiopulmonary failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiovascular disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myocardial necrosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinus bradycardia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wolff-Parkinson-White syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Acute disseminated encephalomyelitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

1 / 205 (0.49%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Axonal neuropathy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Brain oedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Central nervous system lesion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral atrophy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Coma

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Demyelination

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dysgeusia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalitis autoimmune

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalopathy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Facial paralysis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

2 / 205 (0.98%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile convulsion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Generalised tonic-clonic seizure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Haemorrhage intracranial

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Haemorrhagic cerebellar infarction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hemiparesis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic encephalopathy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydrocephalus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoglycaemic seizure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemic seizure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypotonia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Idiopathic intracranial hypertension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic cerebral infarction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Loss of consciousness

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Paraesthesia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraparesis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Partial seizures

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Posterior reversible encephalopathy syndrome

subjects affected / exposed

1 / 313 (0.32%)

2 / 316 (0.63%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 2

0 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Quadriparesis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

12 / 2830 (0.42%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

2 / 296 (0.68%)

2 / 301 (0.66%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

4 / 206 (1.94%)

0 / 205 (0.00%)

2 / 202 (0.99%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 13

0 / 0

0 / 2

0 / 1

0 / 0

1 / 4

0 / 0

2 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Somnolence

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

VIth nerve paralysis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vocal cord paralysis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 313 (0.00%)

2 / 316 (0.63%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bone marrow failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Disseminated intravascular coagulation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Eosinophilia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 7

0 / 2

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Haematotoxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemolytic uraemic syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Haemoperitoneum

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leukopenia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pancytopenia

subjects affected / exposed

1 / 313 (0.32%)

3 / 316 (0.95%)

3 / 2830 (0.11%)

2 / 1308 (0.15%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 1

1 / 4

2 / 3

0 / 2

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Platelet transfusion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary alveolar haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 313 (0.00%)

2 / 316 (0.63%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

2 / 296 (0.68%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

2 / 205 (0.98%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

1 / 2

0 / 0

1 / 1

0 / 0

1 / 2

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombocytopenic purpura

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Hypoacusis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ototoxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

11 / 2830 (0.39%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

2 / 11

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Eye disorders

Accommodation disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Anisocoria

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blindness

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blindness transient

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blindness unilateral

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cycloplegia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Diplopia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Erythema of eyelid

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eyelid ptosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Iridoplegia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

2 / 206 (0.97%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Mydriasis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

5 / 206 (2.43%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

2 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

Ophthalmoplegia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

5 / 206 (2.43%)

1 / 205 (0.49%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 5

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Optic discs blurred

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Opticus atrophy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Papilloedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Periorbital oedema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Photophobia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pupil fixed

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

3 / 206 (1.46%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Strabismus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vision blurred

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Visual impairment

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal adhesions

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal distension

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal hernia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

3 / 206 (1.46%)

0 / 205 (0.00%)

1 / 202 (0.50%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Anal haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

1 / 1308 (0.08%)

7 / 2700 (0.26%)

1 / 296 (0.34%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 7

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cheilitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

1 / 202 (0.50%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis ischaemic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 313 (0.00%)

2 / 316 (0.63%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 313 (0.00%)

2 / 316 (0.63%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

1 / 301 (0.33%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

6 / 206 (2.91%)

0 / 205 (0.00%)

1 / 202 (0.50%)

2 / 975 (0.21%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 3

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

1 / 7

0 / 0

0 / 1

0 / 2

1 / 1

deaths causally related to treatment / all

0 / 0

Diarrhoea haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Duodenitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspepsia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Enterocolitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric pneumatosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric ulcer

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastritis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastritis haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

1 / 2092 (0.05%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

2 / 975 (0.21%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 1

0 / 0

1 / 1

0 / 2

0 / 1

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal inflammation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal necrosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal obstruction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal toxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

2 / 301 (0.66%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Haematemesis

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ileus paralytic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal ischaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

1 / 301 (0.33%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

3 / 205 (1.46%)

0 / 202 (0.00%)

2 / 975 (0.21%)

3 / 3566 (0.08%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 1

0 / 2

0 / 0

0 / 3

0 / 0

0 / 2

2 / 3

deaths causally related to treatment / all

0 / 0

Intestinal perforation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intussusception

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestine perforation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mechanical ileus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Melaena

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mucosal inflammation

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

4 / 2830 (0.14%)

5 / 1308 (0.38%)

0 / 2700 (0.00%)

7 / 296 (2.36%)

10 / 301 (3.32%)

14 / 1804 (0.78%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

1 / 4

1 / 5

0 / 0

1 / 7

1 / 10

0 / 14

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neurogenic bowel

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenic colitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oesophageal stenosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oesophagitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oral pain

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatic pseudocyst

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paralytic ileus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumatosis intestinalis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Rectal haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Severe diarrhoea

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

2 / 301 (0.66%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Stomatitis

subjects affected / exposed

2 / 313 (0.64%)

2 / 316 (0.63%)

0 / 2830 (0.00%)

5 / 1308 (0.38%)

0 / 2700 (0.00%)

5 / 296 (1.69%)

1 / 301 (0.33%)

8 / 1804 (0.44%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

1 / 2

3 / 3

0 / 0

4 / 7

0 / 0

1 / 5

0 / 1

0 / 8

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Stomatitis haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Volvulus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Volvulus of small bowel

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

2 / 301 (0.66%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

1 / 313 (0.32%)

6 / 316 (1.90%)

6 / 2830 (0.21%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

1 / 301 (0.33%)

6 / 1804 (0.33%)

1 / 2092 (0.05%)

2 / 200 (1.00%)

6 / 206 (2.91%)

3 / 205 (1.46%)

0 / 202 (0.00%)

1 / 975 (0.10%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

1 / 1

2 / 6

0 / 6

0 / 0

0 / 1

0 / 0

0 / 1

1 / 6

0 / 1

0 / 2

1 / 7

2 / 3

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

Jejunostomy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary obstruction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholestasis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic cytolysis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic displacement

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic failure

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic function abnormal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic infarction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatitis cholestatic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatomegaly

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatotoxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

3 / 301 (1.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydrocholecystis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Liver disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Portal vein thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Venoocclusive disease

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

8 / 296 (2.70%)

3 / 301 (1.00%)

33 / 1804 (1.83%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

3 / 8

1 / 3

12 / 34

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Venoocclusive liver disease

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

7 / 296 (2.36%)

0 / 301 (0.00%)

43 / 1804 (2.38%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

3 / 3566 (0.08%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

1 / 7

0 / 0

23 / 46

0 / 0

1 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

1 / 2

0 / 0

Skin and subcutaneous tissue disorders

Dermatitis exfoliative

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Erythema

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rash

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

2 / 200 (1.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Rash papular

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin exfoliation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin toxicity

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin ulcer

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urticaria

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

6 / 2830 (0.21%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 6

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Chronic kidney disease

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cystitis haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haematuria

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemolytic uraemic syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

IgA nephropathy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nephritis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Nephropathy toxic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

3 / 301 (1.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Nephrotic syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Neurogenic bladder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oliguria

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Proteinuria

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal failure

subjects affected / exposed

5 / 313 (1.60%)

2 / 316 (0.63%)

33 / 2830 (1.17%)

1 / 1308 (0.08%)

6 / 2700 (0.22%)

0 / 296 (0.00%)

7 / 301 (2.33%)

5 / 1804 (0.28%)

1 / 2092 (0.05%)

1 / 200 (0.50%)

6 / 206 (2.91%)

2 / 205 (0.98%)

3 / 202 (1.49%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

2 / 5

1 / 2

6 / 34

1 / 1

1 / 6

0 / 0

3 / 7

1 / 5

0 / 1

1 / 1

1 / 7

0 / 2

3 / 3

1 / 1

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Renal haemorrhage

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal impairment

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Renal tubular acidosis

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal tubular disorder

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal tubular dysfunction

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Renal vein thrombosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal-limited thrombotic microangiopathy

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary retention

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Adrenal insufficiency

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Inappropriate antidiuretic hormone secretion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthritis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acinetobacter infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Adenovirus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

3 / 1804 (0.17%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Appendicitis

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis bacterial

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspergillus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacillus bacteraemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacillus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacterial infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bacterial sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Brain abscess

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bronchiolitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchopulmonary aspergillosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Candida infection

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 4

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Candida sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Citrobacter infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium colitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cystitis haemorrhagic

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cystitis klebsiella

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cytomegalovirus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Device related bacteraemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

1 / 313 (0.32%)

1 / 316 (0.32%)

6 / 2830 (0.21%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

1 / 6

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Disseminated aspergillosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterobacter infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

2 / 200 (1.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Enterococcal infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterococcal sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterocolitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epstein-Barr virus infection reactivation

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Erysipelas

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia infection

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia pyelonephritis

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

1 / 296 (0.34%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia urinary tract infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

9 / 313 (2.88%)

20 / 316 (6.33%)

30 / 2830 (1.06%)

19 / 1308 (1.45%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

1 / 301 (0.33%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

3 / 975 (0.31%)

3 / 3566 (0.08%)

occurrences causally related to treatment / all

6 / 17

16 / 42

15 / 44

20 / 29

0 / 0

0 / 1

1 / 1

0 / 0

1 / 3

2 / 4

deaths causally related to treatment / all

0 / 0

Fungal infection

subjects affected / exposed

3 / 313 (0.96%)

1 / 316 (0.32%)

7 / 2830 (0.25%)

0 / 1308 (0.00%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

1 / 301 (0.33%)

6 / 1804 (0.33%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

3 / 3566 (0.08%)

occurrences causally related to treatment / all

0 / 3

0 / 2

1 / 7

0 / 0

1 / 2

0 / 0

0 / 1

0 / 6

0 / 0

1 / 1

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

Fungal sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Fusarium infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis adenovirus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis clostridial

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis rotavirus

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

2 / 1308 (0.15%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastroenteritis salmonella

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

3 / 200 (1.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Gastroenteritis viral

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

H1N1 influenza

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemophilus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatitis C

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes simplex

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes virus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes zoster

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Herpes zoster meningoencephalitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileal gangrene

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

8 / 2830 (0.28%)

1 / 1308 (0.08%)

2 / 2700 (0.07%)

1 / 296 (0.34%)

2 / 301 (0.66%)

8 / 1804 (0.44%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

2 / 975 (0.21%)

8 / 3566 (0.22%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 8

0 / 1

0 / 2

0 / 1

0 / 2

0 / 8

0 / 0

0 / 1

0 / 0

0 / 2

0 / 9

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Influenza

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Klebsiella infection

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Klebsiella sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection viral

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis viral

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Moraxella infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oral candidiasis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oral herpes

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oral infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Osteomyelitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Osteomyelitis fungal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parainfluenzae virus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parvovirus infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pharyngitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

1 / 1308 (0.08%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumococcal sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis jirovecii infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis jirovecii pneumonia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

2 / 2092 (0.10%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

1 / 1

1 / 2

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

3 / 301 (1.00%)

2 / 1804 (0.11%)

2 / 2092 (0.10%)

0 / 200 (0.00%)

1 / 206 (0.49%)

1 / 205 (0.49%)

1 / 202 (0.50%)

1 / 975 (0.10%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 5

0 / 0

1 / 3

2 / 2

0 / 2

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Pneumonia adenoviral

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia bacterial

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia cytomegaloviral

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia fungal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia pneumococcal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia staphylococcal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pseudomembranous colitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pseudomonal sepsis

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

3 / 2830 (0.11%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pseudomonas infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 4

0 / 0

1 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

3 / 313 (0.96%)

7 / 316 (2.22%)

11 / 2830 (0.39%)

4 / 1308 (0.31%)

2 / 2700 (0.07%)

0 / 296 (0.00%)

0 / 301 (0.00%)

2 / 1804 (0.11%)

4 / 2092 (0.19%)

4 / 200 (2.00%)

14 / 206 (6.80%)

4 / 205 (1.95%)

7 / 202 (3.47%)

7 / 975 (0.72%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 3

3 / 8

3 / 13

1 / 4

0 / 2

0 / 0

0 / 3

0 / 5

1 / 19

1 / 5

7 / 10

2 / 10

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory syncytial virus infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection fungal

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Salmonellosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

3 / 313 (0.96%)

12 / 316 (3.80%)

30 / 2830 (1.06%)

2 / 1308 (0.15%)

5 / 2700 (0.19%)

4 / 296 (1.35%)

6 / 301 (1.99%)

13 / 1804 (0.72%)

8 / 2092 (0.38%)

4 / 200 (2.00%)

7 / 206 (3.40%)

3 / 205 (1.46%)

2 / 202 (0.99%)

10 / 975 (1.03%)

4 / 3566 (0.11%)

occurrences causally related to treatment / all

1 / 4

3 / 12

9 / 40

0 / 3

0 / 6

3 / 6

1 / 6

3 / 13

0 / 8

0 / 5

4 / 10

0 / 3

1 / 2

0 / 10

1 / 5

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Septic shock

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

5 / 2830 (0.18%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

6 / 1804 (0.33%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

4 / 3566 (0.11%)

occurrences causally related to treatment / all

0 / 0

2 / 5

0 / 0

0 / 1

0 / 6

0 / 0

0 / 5

0 / 0

1 / 4

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Serratia infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sinusitis aspergillus

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Splenic abscess

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

4 / 2830 (0.14%)

1 / 1308 (0.08%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

2 / 2092 (0.10%)

2 / 200 (1.00%)

2 / 206 (0.97%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 4

1 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Staphylococcal sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

9 / 2830 (0.32%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 9

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Stenotrophomonas infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Stomatitis

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Streptococcal infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Streptococcal sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Systemic candida

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Systemic inflammatory response syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Systemic viral infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tonsillitis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper respiratory tract infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

0 / 206 (0.00%)

1 / 205 (0.49%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Varicella

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

2 / 2830 (0.07%)

2 / 1308 (0.15%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

1 / 3

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular device infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

4 / 2830 (0.14%)

2 / 1308 (0.15%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

2 / 205 (0.98%)

1 / 202 (0.50%)

0 / 975 (0.00%)

2 / 3566 (0.06%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Viral infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound infection

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterobacter sepsis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

1 / 296 (0.34%)

1 / 301 (0.33%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

1 / 2700 (0.04%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Electrolyte depletion

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Failure to thrive

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Feeding intolerance

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fluid retention

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypercalcaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

1 / 200 (0.50%)

1 / 206 (0.49%)

0 / 205 (0.00%)

3 / 202 (1.49%)

8 / 975 (0.82%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 3

3 / 9

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

1 / 975 (0.10%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperuricaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

1 / 202 (0.50%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoalbuminaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

1 / 206 (0.49%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

1 / 3566 (0.03%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malnutrition

subjects affected / exposed

0 / 313 (0.00%)

1 / 316 (0.32%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolic acidosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

1 / 301 (0.33%)

1 / 1804 (0.06%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolic alkalosis

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

1 / 2092 (0.05%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Refeeding syndrome

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

1 / 2830 (0.04%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour lysis syndrome

subjects affected / exposed

1 / 313 (0.32%)

0 / 316 (0.00%)

2 / 2830 (0.07%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

IND (randomised COJEC)

IND (randomised N7)

IND (not randomised)

TVD.

SURGERY

MAT (randomised BUMEL)

MAT (randomised CEM)

MAT (not randomised)

RADIOTHERAPY

MRD (R2 randomised GD2 only)

MRD (R2 randomised GD2 + IL-2)

MRD (R4 randomised GD2 only)

MRD (R4 randomised GD2 + IL-2)

MRD (not randomised)

Other occ. phase, missing

Total subjects affected by non serious adverse events

subjects affected / exposed

0 / 313 (0.00%)

0 / 316 (0.00%)

0 / 2830 (0.00%)

0 / 1308 (0.00%)

0 / 2700 (0.00%)

0 / 296 (0.00%)

0 / 301 (0.00%)

0 / 1804 (0.00%)

0 / 2092 (0.00%)

0 / 200 (0.00%)

0 / 206 (0.00%)

0 / 205 (0.00%)

0 / 202 (0.00%)

0 / 975 (0.00%)

0 / 3566 (0.00%)

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Were there any global substantial amendments to the protocol? Yes

01 Nov 2005

Amendment 1

10 Mar 2006

Amendment 2

31 Jul 2007

Amendment 3

01 Jul 2009

Amendment 4

01 Jun 2011

Amendment 5, HR-NBL1.5 SIOPEN

01 Aug 2013

Amendment 6, HR-NBL1.6 SIOPEN

04 Apr 2014

Amendment 7, HR-NBL1.7 SIOPEN

15 Sep 2017

Amendment 8, HR-NBL1.8 SIOPEN

12 Dec 2022

Amendment 9, HR-NBL1.9 SIOPEN

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 3-years Event-free survival - EFS

Primary: 3-years Event-free survival - EFS

Secondary: 3-years Overall survival - OS

Secondary: 3-years Overall survival - OS

Secondary: 3-years Cumulative incidence of relapse - CIR

Secondary: 3-years Cumulative incidence of relapse - CIR

Secondary: 3-years Non-relapse mortality - NRM

Secondary: 3-years Non-relapse mortality - NRM

Secondary: 3-years Cumulative incidence of secondary malignancies

Secondary: 3-years Cumulative incidence of secondary malignancies

Other pre-specified: Number of febrile episodes per course

Other pre-specified: Number of febrile episodes per course

Adverse events

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Substantial protocol amendments (globally)

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Online references

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Clinical trials

Clinical Trial Results: High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 3-years Event-free survival - EFS

Primary: 3-years Event-free survival - EFS

Secondary: 3-years Overall survival - OS

Secondary: 3-years Overall survival - OS

Secondary: 3-years Cumulative incidence of relapse - CIR

Secondary: 3-years Cumulative incidence of relapse - CIR

Secondary: 3-years Non-relapse mortality - NRM

Secondary: 3-years Non-relapse mortality - NRM

Secondary: 3-years Cumulative incidence of secondary malignancies

Secondary: 3-years Cumulative incidence of secondary malignancies

Other pre-specified: Number of febrile episodes per course

Other pre-specified: Number of febrile episodes per course

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN)