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Clinical Trial Results:
A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Pediatric Subjects with Acute Leukemias Undergoing Myeloblative Therapy and Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Summary
EudraCT number	2015-002526-39
Trial protocol	Outside EU/EEA
Global end of trial date	12 May 2011

Results information
Results version number	v1(current)
This version publication date	27 Nov 2016
First version publication date	27 Nov 2016
Other versions

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

20010133

ISRCTN number

US NCT number

NCT00460421

WHO universal trial number (UTN)

Other trial identifiers

IND: 6370

Sponsor organisation name

Swedish Orphan Biovitrum AB (publ)

Sponsor organisation address

Tomtebodavägen 23, Stockholm, Sweden, 112 76

Public contact

Ida Gunnarsson, Swedish Orphan Biovitrum AB (publ), +46 8697 38 78, ida.gunnarsson@sobi.com

Scientific contact

Ida Gunnarsson, Swedish Orphan Biovitrum AB (publ), +46 8697 38 78, ida.gunnarsson@sobi.com

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?

Yes

Analysis stage

Final

Date of interim/final analysis

12 May 2011

Is this the analysis of the primary completion data?

Yes

Primary completion date

26 Jan 2010

Global end of trial reached?

Yes

Global end of trial date

12 May 2011

Was the trial ended prematurely?

Main objective of the trial

To determine a safe and tolerable dose of palifermin in pediatric subjects of different age groups when administered once daily for 3 consecutive days before and 3 consecutive days after a myeloablative chemo-radiotherapy conditioning regimen with allogeneic HSCT.

Protection of trial subjects

The study was carried out in compliance with the protocol, the principles laid down in the Declaration of Helsinki (1996 Version), in accordance with the International Conference on Harmonization (ICH) Harmonised Tripartite Guideline for Good Clinical Practice (GCP) and in accordance with applicable regulatory requirements. Essential documents will be retained in accordance with ICH GCP.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Aug 2006

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 27

Worldwide total number of subjects

EEA total number of subjects

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)

Children (2-11 years)

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

Screening details

After signing the informed consent/giving assent, subjects were screened for eligibility to receive the protocol-specific chemotherapy regimens. Screening tests and procedures were performed within 30 days of study enrollment unless otherwise stated. Eligible subjects received the first dose of palifermin within 72 hours after enrollment.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

40 μg/kg/day palifermin: 1-2 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

Palifermin was administered by IV bolus injection (40, 60, or 80 μg/kg/day depending upon dose cohort) once daily for 3 consecutive days before the start of the conditioning regimen and after HSCT (Day -10, -9, -8 and Day 0, +1, +2, respectively).

60 μg/kg/day palifermin: 1-2 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

80 μg/kg/day palifermin: 1-2 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

40 μg/kg/day palifermin: 3-11 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

60 μg/kg/day palifermin: 3-11 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

80 μg/kg/day palifermin: 3-11 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

40 μg/kg/day palifermin: 12-16 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

60 μg/kg/day palifermin: 12-16 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

80 μg/kg/day palifermin: 12-16 years

Arm description

Arm type

Experimental

Investigational medicinal product name

Palifermin

Investigational medicinal product code

Other name

Kepivance

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intravenous bolus use

Dosage and administration details

Number of subjects in period 1	40 μg/kg/day palifermin: 1-2 years	60 μg/kg/day palifermin: 1-2 years	80 μg/kg/day palifermin: 1-2 years	40 μg/kg/day palifermin: 3-11 years	60 μg/kg/day palifermin: 3-11 years	80 μg/kg/day palifermin: 3-11 years	40 μg/kg/day palifermin: 12-16 years	60 μg/kg/day palifermin: 12-16 years	80 μg/kg/day palifermin: 12-16 years
Started	3	3	3	3	3	3	3	3	3
Completed	3	3	3	3	3	3	3	3	3

Baseline characteristics

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Reporting group title

40 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group values	40 μg/kg/day palifermin: 1-2 years	60 μg/kg/day palifermin: 1-2 years	80 μg/kg/day palifermin: 1-2 years	40 μg/kg/day palifermin: 3-11 years	60 μg/kg/day palifermin: 3-11 years	80 μg/kg/day palifermin: 3-11 years	40 μg/kg/day palifermin: 12-16 years	60 μg/kg/day palifermin: 12-16 years	80 μg/kg/day palifermin: 12-16 years	Total
Number of subjects	3	3	3	3	3	3	3	3	3	27
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	2	1	3	0	0	0	0	0	0	6
Children (2-11 years)	1	2	0	3	3	3	0	0	0	12
Adolescents (12-17 years)	0	0	0	0	0	0	3	3	3	9
Adults (18-64 years)	0	0	0	0	0	0	0	0	0	0
From 65-84 years	0	0	0	0	0	0	0	0	0	0
85 years and over	0	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	0	0	2	1	3	2	2	1	1	12
Male	3	3	1	2	0	1	1	2	2	15

Subject analysis set title

Safety Analysis subset

Subject analysis set type

Safety analysis

Subject analysis set description

This set consists of all subjects who receive at least one dose of palifermin.

Subject analysis sets values	Safety Analysis subset
Number of subjects	27
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	6
Children (2-11 years)	12
Adolescents (12-17 years)	9
Adults (18-64 years)	0
From 65-84 years	0
85 years and over	0
Age continuous
Units:
	±
Gender categorical
Units: Subjects
Female	12
Male	15

End points

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Reporting group title

40 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 12-16 years

Reporting group description

Subject analysis set title

Safety Analysis subset

Subject analysis set type

Safety analysis

Subject analysis set description

This set consists of all subjects who receive at least one dose of palifermin.

Primary: Incidence of dose limiting toxicities (DLTs)

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End point title

Incidence of dose limiting toxicities (DLTs) ^[1]

End point description

End point type

Primary

End point timeframe

to be completed

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses have been performed.

End point values	40 μg/kg/day palifermin: 1-2 years	60 μg/kg/day palifermin: 1-2 years	80 μg/kg/day palifermin: 1-2 years	40 μg/kg/day palifermin: 3-11 years	60 μg/kg/day palifermin: 3-11 years	80 μg/kg/day palifermin: 3-11 years	40 μg/kg/day palifermin: 12-16 years	60 μg/kg/day palifermin: 12-16 years	80 μg/kg/day palifermin: 12-16 years
Number of subjects analysed	3	3	3	3	3	3	3	3	3
Units: Number of patients
Yes	0	0	0	0	0	0	0	0	0
No	3	3	3	3	3	3	3	3	3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From start of treatment until 30 days post transplant (Day –10 to Day +30).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

12.0

Reporting group title

40 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 1-2 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 3-11 years

Reporting group description

Reporting group title

40 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

60 μg/kg/day palifermin: 12-16 years

Reporting group description

Reporting group title

80 μg/kg/day palifermin: 12-16 years

Reporting group description

Serious adverse events	40 μg/kg/day palifermin: 1-2 years	60 μg/kg/day palifermin: 1-2 years	80 μg/kg/day palifermin: 1-2 years	40 μg/kg/day palifermin: 3-11 years	60 μg/kg/day palifermin: 3-11 years	80 μg/kg/day palifermin: 3-11 years	40 μg/kg/day palifermin: 12-16 years	60 μg/kg/day palifermin: 12-16 years	80 μg/kg/day palifermin: 12-16 years
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Investigations
Urine output decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Venoocclusive disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebral hemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Convulsion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hemorrhage Intracranial
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Ascites
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal hemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Dyspnea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Enterococcal infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	40 μg/kg/day palifermin: 1-2 years	60 μg/kg/day palifermin: 1-2 years	80 μg/kg/day palifermin: 1-2 years	40 μg/kg/day palifermin: 3-11 years	60 μg/kg/day palifermin: 3-11 years	80 μg/kg/day palifermin: 3-11 years	40 μg/kg/day palifermin: 12-16 years	60 μg/kg/day palifermin: 12-16 years	80 μg/kg/day palifermin: 12-16 years
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)
Vascular disorders
Flushing
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	0 / 3 (0.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	0 / 3 (0.00%)
occurrences all number	11	2	6	3	4	0	4	4	0
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)
occurrences all number	0	0	1	1	1	4	0	2	1
Hypoperfusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Venoocclusive disease
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Surgical and medical procedures
Pallor
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Venous thrombosis limb
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
General disorders and administration site conditions
Application site rash
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Catheter related complication
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)
occurrences all number	1	0	2	0	0	1	0	0	3
Catheter site erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Catheter site pain
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	2	0	2	0
Chills
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	1	0	0	0	0	0	0	1	1
Face oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1	1	0	0	0	0	1
Fatigue
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)
occurrences all number	0	0	2	0	0	2	2	2	1
Generalised oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypothermia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	1	0	0	1	0	0	1
Mucosal inflammation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Oedema
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	0	1	0	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	2	0	2	0	0	0
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)
occurrences all number	0	0	4	0	0	0	0	0	2
Pyrexia
subjects affected / exposed	3 / 3 (100.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	3 / 3 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)
occurrences all number	12	4	1	6	4	3	5	5	4
Immune system disorders
Acute graft versus host disease in intestine
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Acute graft versus host disease in skin
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	1	0	0	2	0	0	1
Drug hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Engraftment syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Genital burning sensation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Genital discomfort
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Metrorrhagia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Perineal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Scrotal erythema
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	0	0	0	0	0	0	1
Scrotal swelling
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Testicular pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	0
Respiratory, thoracic and mediastinal disorders
Vulvovaginal pruritus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Atelectasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0
Cough
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	1	2	3	1	2	3	0	1	1
Dyspnoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 3 (100.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	1	2	3	2	1
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Lung infiltration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	3 / 3 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	2 / 3 (66.67%)
occurrences all number	1	0	0	2	1	3	2	4	2
Oropharyngeal plaque
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	2	0	0	0
Rales
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	0	0	1	0
Tachypnoea
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	2	0	1	1	0	0	0
Upper respiratory tract congestion
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	1	0	0	0	0
Wheezing
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	1	1	0	0	0	1	1	1
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1	0	1	3	1	0	1
Confusional state
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Insomnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 3 (66.67%)
occurrences all number	0	0	0	0	0	0	1	1	2
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	5	0	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	5	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	4	0	0	0	0	5	0
Blood pressure increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Blood sodium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Carbon dioxide decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Culture urine positive
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Cytomegalovirus test positive
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Fungus stool identified
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Occult blood
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Occult blood positive
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0
Oxygen saturation decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Transaminases increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Urine output decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Weight decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	1	0	0	5
Weight increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	3	0	0	2	0	2	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0
Excoriation
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	1	1	0	1	1	0	0	1	0
Failure to capture
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Head injury
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Procedural hypertension
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Refractoriness to platelet transfusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Wound
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Cardiac disorders
Bradycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	1	1	1	1	1	0	0
Cardiac failure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Nervous system disorders
Dyskinesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Tremor
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Blood and lymphatic system disorders
Febrile neutropenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	1	0	1	0	0	0	0
Haemolysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Ear and labyrinth disorders
Auricular swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Ear pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	1	1
Eye disorders
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)	3 / 3 (100.00%)	2 / 3 (66.67%)
occurrences all number	1	0	2	2	2	3	4	4	3
Abdominal pain upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Abnormal faeces
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	2	0	0	0	0	0	0
Colitis
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	2	0	0	2	1	1
Diarrhoea
subjects affected / exposed	3 / 3 (100.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	2 / 3 (66.67%)
occurrences all number	3	2	2	1	2	2	3	3	2
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	3	2	0	0
Faeces discoloured
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0
Gastric hypomotility
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Gastritis
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Gingival hyperplasia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	1	0	0	1
Haematemesis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Lip disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Lip dry
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0
Lip exfoliation
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Lip swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Mouth haemorrhage
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Nausea
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)
occurrences all number	1	2	2	2	3	3	3	6	6
Oesophagitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	1	0	1
Oral mucosal erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Oral pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0
Perianal erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
Proctalgia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	1	0	2	1	0	0
Saliva altered
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Vomiting
subjects affected / exposed	3 / 3 (100.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)
occurrences all number	3	3	2	3	3	2	3	6	4
Hepatobiliary disorders
Cholelithiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hepatomegaly
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	5	1	0	0	1	1	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	1	1	0
Blister
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Dermatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Dermatitis diaper
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	0	0	0	0	0	1
Erythema
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	2	0	1	0	0	0	0	1	0
Ingrowing nail
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0
Petechiae
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0
Pigmentation disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 3 (100.00%)
occurrences all number	2	1	2	2	2	6	1	0	4
Rash
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	1 / 3 (33.33%)	3 / 3 (100.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 3 (66.67%)
occurrences all number	1	0	3	4	2	3	1	1	2
Rash erythematous
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Rash generalised
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Skin discolouration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Skin disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	1	0
Skin exfoliation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Skin hyperpigmentation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Skin irritation
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0
Skin ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Urticaria
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	0	0	0	0	0	0	1
Swelling face
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	1	0	0	1
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	1	0	0	1	0	0
Incontinence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Proteinuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Renal tubular acidosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Back pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1	0	2	0	0	1
Bone pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
Groin pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Muscle contracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Muscular weakness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 3 (100.00%)	2 / 3 (66.67%)
occurrences all number	0	0	0	0	1	1	1	4	2
Pain in jaw
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0	0
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	3 / 3 (100.00%)
occurrences all number	0	0	0	0	1	3	2	3	4
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	2	0
Dysgeuesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Lethargy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0
Infections and infestations
Acinetobacter bacteraemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Actinomycosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Alpha haemolytic streptococcal infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	1	0	0	0	0	0
Bacteraemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Clostridium difficile colitis
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	1	0	0	0	0	0
Cytomegalovirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Enterococcal bacteraemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Enterococcal infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Enterococcal sepsis
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Fungal infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0
Infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Parainfluenzae virus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Parotitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	2	0	1
Penile infection
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pneumonia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0
Respiratory syncytial virus infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Rotavirus infection
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	0	1	0	0
Staphylococcal bacteraemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Staphylococcal infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 3 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	3	0	0	2
Urinary tract infection enterococcal
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	1	0	0	0	0	0	0	1
Viral infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Anorexia
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	3 / 3 (100.00%)	1 / 3 (33.33%)	3 / 3 (100.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)
occurrences all number	1	2	3	4	1	3	4	2	3
Acidosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	7	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	1	0	0	0	1
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1
Fluid overload
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Fluid retention
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	1	0	0	1	0	0	2	0	1
Hypercalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 3 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	3	0	0	3	1	0	0
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0
Hypermagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
hypernatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)
occurrences all number	0	0	1	0	0	3	0	0	2
Hypoglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	4	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 3 (100.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	2	9	0	0	3	0	1	2
Hypomagnesaemia
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 3 (100.00%)
occurrences all number	1	0	2	1	0	2	1	1	3
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	4	0	0	2	0	0	1
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)
occurrences all number	0	0	0	0	0	1	0	0	3

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Were there any global substantial amendments to the protocol? Yes

12 May 2006

Protocol amendment 1, dated 12 May 2006, was introduced before enrollment started and made changes based on feedback from the Oncology Drug Advisory Committee (ODAC) pediatric subcommittee meeting held on 20 October 2005, and the FDA following their review of the 20010133 draft protocol. This draft protocol was submitted in response to the ODAC pediatric subcommittee meeting.

12 Mar 2007

Modified the eligibility criteria to exclude subjects with a known sensitivity to any E. coli-derived products with the exception of known grade 1–2 allergic reactions to L-asparaginase [subjects with allergies to grade 3 and 4 L-asparaginase were to be excluded] • Updated the contact information for the Pediatric Blood and Marrow Transplant Consortium • Updated key sponsor contact information • Modified rounding instructions for palifermin preparation and administration in protocol Appendix E due to the small administration volumes used in this pediatric study • Corrected blood volume requirements in protocol Section 7.1.3 • Clarified the instructions to sites regarding concomitant use of palifermin and heparin • Clarified the interpretation of protocol Appendix H as TBI guidelines • Modified the definition of treatment period throughout the protocol as Treatment Period/Safety Assessment: until 30 days post transplant (Day –10 to Day +30) • Modified the definition of engraftment throughout the protocol to ANC recovery (ANC >0.5 x 109/L for 3 consecutive days) • Corrected the IBW calculation in protocol Appendix F • Updated references throughout the protocol • Updated the information on blood volume collection in the ICF • Corrected typographical and formatting errors throughout the protocol

15 Dec 2008

Protocol amendment 3, dated 15 December 2008, was required to take account of the acquisition of the product Kepivance (palifermin) by Biovitrum AB (now Sobi) from Amgen Inc. The following changes to the protocol were made: • Described the change in sponsorship from Amgen Inc. to Biovitrum AB • Removed Appendices C (the SAE Form) and D (the Pregnancy Notification Worksheet). These forms were provided separately and not as a part of the study protocol. Appendix numbering was changed due to this deletion. • Updated the ICF in accordance with the Amgen QSUR Q3 2008 to include palmar-plantar erythrodysesthesia (PPES) and vaginal edema and erythema

28 Jan 2011

Protocol amendment 4, dated 28 January 2011, made the following changes: • Ceased collection of long term follow-up data after the last enrolled subject had completed the Day +100 follow-up. • References to a follow-up ‘for a maximum of 10 years’ were amended to ‘until end of study’. • Altered Sponsor name from Biovitrum to Swedish Orphan Biovitrum throughout protocol and updated relevant related information, such as Study Manager and Medical Director name and contact address.

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 Trial Results:
A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Pediatric Subjects with Acute Leukemias Undergoing Myeloblative Therapy and Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

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Clinical Trial Results: A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Pediatric Subjects with Acute Leukemias Undergoing Myeloblative Therapy and Allogeneic Hematopoietic Stem Cell Transplant (HSCT)

Trial information

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Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Incidence of dose limiting toxicities (DLTs)

Primary: Incidence of dose limiting toxicities (DLTs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1 Dose-escalation Study to Evaluate the Safety and Pharmacokinetics (PK) of Palifermin in Pediatric Subjects with Acute Leukemias Undergoing Myeloblative Therapy and Allogeneic Hematopoietic Stem Cell Transplant (HSCT)