Clinical Trial Results:
An open Phase I trial to investigate the maximum tolerated dose, safety, efficacy and pharmacokinetics of BI 811283 in combination with cytarabine in patients with previously untreated or relapsed/refractory acute myeloid leukaemia ineligible for intensive treatment

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2007-005684-10
Trial protocol	ES AT
Global end of trial date	05 Mar 2014

Results information
Results version number	v2(current)
This version publication date	02 Jul 2016
First version publication date	01 Aug 2015
Other versions	v1 (removed from public view)
Version creation reason	Correction of full data set Data correction due to a system error in EudraCT- Results

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

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

1247.3

ISRCTN number

US NCT number

NCT00632749

WHO universal trial number (UTN)

Sponsor organisation name

Boehringer Ingelheim

Sponsor organisation address

Binger Strasse 173 , Ingelheim am Rhein, Germany, 55216

Public contact

QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim Pharma GmbH & Co. KG, +1 800 243 0127, clintriage.rdg@boehringer-ingelheim.com

Scientific contact

QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim Pharma GmbH & Co. KG, +1 800 243 0127, clintriage.rdg@boehringer-ingelheim.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?

Analysis stage

Final

Date of interim/final analysis

12 May 2014

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Mar 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

In this phase I trial, two schedules of BI 811283 in combination with LD-Ara-C will be investigated. The dose of BI 811283 will be escalated to determine the maximum tolerated dose (MTD) of the two dosing schedules of BI 811283 in combination with LDAra-C.

Protection of trial subjects

Only subjects that met all study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jun 2008

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Germany: 72

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

Top of page

Recruitment details

Out of 72 patients enrolled, 68 entered the study, and 64 were treated with the study treatment. One patient was on trial receiving medication for 2.5 years after the primary database lock date due to benefit.

Screening details

All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subjects) met all inclusion/exclusion criteria. Subjects were not to be entered into the trial to receive trial medication if any one of the specific entry criteria were violated.

Period 1 title

Treatment period (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

Non-randomized, uncontrolled design.

Are arms mutually exclusive

Yes

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Arm description

5 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

Arm description

15 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion cytarabine: subcutaneous injection. Two patients were entered in the 15mg BI 811283+ 20mg cytarabine- Treatment Schedule A cohort, however those two patients were not treated. Consequently, even though the actual number of subjects that started is 5, only 3 were reported to ensure consistent reporting with baseline characteristics that includes only treated patients.

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

15 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Arm description

30 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

30 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Arm description

60 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

60 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Arm description

100 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

100 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Arm description

120 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment Schedule A: BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion cytarabine: subcutaneous injection. One patient was entered in the 120mg BI 811283+ 20 mg cytarabine- Treatment Schedule A cohort, however this patient was not treated. Consequently, even though the actual number of subjects that started is 8, only 7 were reported to ensure consistent reporting with baseline characteristics that includes only treated patients.

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

120 mg of BI 811283 administered on days 1+15 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Arm description

5 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion cytarabine: subcutaneous injection. One patient was entered in the 5mg BI 811283+ 20mg cytarabine- Treatment Schedule B cohort, however this patient was not treated. Consequently, even though the actual number of subjects that started is 5, only 4 were reported to ensure consistent reporting with baseline characteristics that includes only treated patients.

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

5 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Arm description

40 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

40 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Arm description

80 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

80 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Arm description

160 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

160 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Arm description

240 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

240 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Arm description

300 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

300 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Arm description

360 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

360 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Arm description

420 mg of BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection); Treatment schedule B: BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle); BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection.

Arm type

Experimental

Investigational medicinal product name

BI 811283

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

420 mg of BI 811283 administered on days 1 via 24-hour continuous intravenous infusion

Investigational medicinal product name

Cytarabine

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

20 mg of cytarabine was administered via subcutaneous injection twice daily on Days 1-10 (28-day cycle)

Number of subjects in period 1 ^[1]	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Started	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Adverse event, serious fatal	-	-	-	1	1	2	-	2	1	-	-	-	-	-
Other reason not specified	-	1	-	-	1	-	1	-	-	-	2	1	-	2
Adverse event, non-fatal	1	-	1	-	1	1	-	-	1	-	1	-	1	-
Refuse to continue medication	-	-	-	1	-	-	-	-	-	1	-	-	-	-
Progressive disease	3	2	2	2	4	4	3	2	3	2	4	3	2	4

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Baseline characteristics are based on patients who were entered after successfully completing the screening period and received at least one of the trial medications.

Baseline characteristics

Top of page

Reporting group title

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Reporting group description

Reporting group title

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Reporting group description

Reporting group title

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	Total
Number of subjects	4	3	3	4	7	7	4	4	5	3	7	4	3	6	64
Age categorical
Units: Subjects
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	76 ( 5.8 )	71.3 ( 2.5 )	79.3 ( 8.4 )	77.5 ( 4 )	67.4 ( 9.3 )	72.3 ( 5.1 )	74.3 ( 4.1 )	73.5 ( 6.6 )	79 ( 4.4 )	78.3 ( 4 )	72.3 ( 4.4 )	69.5 ( 11.8 )	63.3 ( 5.1 )	63.3 ( 5.6 )	-
Gender, Male/Female
Units: participants
Female	3	2	2	2	4	3	1	3	2	2	2	2	0	2	30
Male	1	1	1	2	3	4	3	1	3	1	5	2	3	4	34

Subject analysis set title

Treatment Schedule A

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BI 811283 on Days 1 + 15 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle). BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection).The starting dose for BI 811283 was 5 mg, with dose levels of 5, 15, 30, 60, 100 and 120 mg used in Schedule A.BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection

Subject analysis set title

Treatment schedule B

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subjects received BI 811283 on Day 1 in combination with cytarabine 20 mg twice daily on Days 1-10 (28-day cycle).BI 811283 (preconcentrate for infusion after dilution) in combination with cytarabine (solution for injection).The starting dose for BI 811283 was 5 mg, with dose levels of 5, 40, 80, 160, 240, 300, 360 and 420 mg being used in Schedule B.BI 811283: 24-hour continuous intravenous infusion Cytarabine: subcutaneous injection.

Subject analysis sets values	Treatment Schedule A	Treatment schedule B
Number of subjects	28	36
Age categorical
Units: Subjects
Age Continuous \|
Units: years
arithmetic mean (standard deviation)	73 ( 7.3 )	71.5 ( 7.8 )
Gender, Male/Female
Units: participants
Female	16	14
Male	12	22

End points

Top of page

Reporting group title

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Reporting group description

Reporting group title

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

Reporting group description

Reporting group title

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Reporting group title

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Reporting group description

Subject analysis set title

Treatment Schedule A

Subject analysis set type

Intention-to-treat

Subject analysis set description

Subject analysis set title

Treatment schedule B

Subject analysis set type

Intention-to-treat

Subject analysis set description

Primary: The maximum tolerated dose (MTD) of 2 schedules of BI 811283 in combination with cytarabine.

Top of page

End point title

The maximum tolerated dose (MTD) of 2 schedules of BI 811283 in combination with cytarabine. ^[1]

End point description

The MTD was defined as the highest dose at which 6 patients were treated and less than 2 patients who experienced a dose limiting toxicities (DLT) within the first cycle of treatment.The MTD was defined based on safety data from the first cycle only. It was determined using a standard “3 + 3 design with de-escalation”. Treated set (TS): All patients who received at least one single dose of trial medication (BI 811283 or cytarabine) were considered for evaluation. 99999= Due to the early termination of study for strategic reasons, the MDT was not reached in schedule B

End point type

Primary

End point timeframe

up to 28 days of treatment

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: All analyses in this study are descriptive and exploratory by nature,thus no statistical analyses for this primary endpoint are specified.

End point values	Treatment Schedule A	Treatment schedule B
Number of subjects analysed	28 ^[2]	36 ^[3]
Units: mg	100	99999

Notes
[2] - TS
[3] - TS

No statistical analyses for this end point

Secondary: Response (complete remission [CR], complete remission with incomplete blood count recovery [CRi])

Top of page

End point title

Response (complete remission [CR], complete remission with incomplete blood count recovery [CRi])

End point description

Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria): The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment.Complete remission (CR): morphologically leukaemia free state (i.e. bone marrow with < 5% blasts by morphologic criteria and no Auer rods, no evidence of extramedullary leukaemia) and absolute neutrophil count ≥ 1,000/μL and platelets > 100,000/μL.Complete remission with incomplete blood count recovery (“incomplete” CR, CRi).All of the above criteria for CR had to be met, except that neutrophils < 1,000/μL or platelets < 100,000/μL in the blood. Patients in TS were considered.

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20Oct2011, Up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: participants
CR	0	0	0	1	0	1	1	0	1	1	1	0	1	0
CRi	0	0	0	0	0	0	0	0	0	0	0	0	1	0

No statistical analyses for this end point

Secondary: Incidence and intensity of AEs graded according to CTCAE (version 3.0)

Top of page

End point title

Incidence and intensity of AEs graded according to CTCAE (version 3.0)

End point description

The severity and timing of AEs indicates how well the treatment regimen was tolerated. Toxicities were evaluated using the common terminology criteria for adverse events (CTCAE) grading scheme. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: participants
CTCAE Grade 1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
CTCAE Grade 2	0	0	1	0	0	0	0	0	0	0	0	0	0	0
CTCAE Grade 3	1	1	0	1	1	0	1	0	0	1	2	1	0	0
CTCAE Grade 4	0	2	2	2	4	3	1	2	3	1	3	1	2	2
CTCAE Grade 5	3	0	0	1	2	4	2	2	2	1	2	2	1	4

No statistical analyses for this end point

Secondary: Incidence of dose limiting toxicity (DLT)

Top of page

End point title

Incidence of dose limiting toxicity (DLT)

End point description

Number of participants with DLT in the first cycle (28 days) for the determination of the maximum tolerated dose (MTD). Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

up to 28 days of treatment

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: participants	0	0	0	0	0	2	1	0	0	0	1	0	1	0

No statistical analyses for this end point

Secondary: Partial Remission

Top of page

End point title

Partial Remission

End point description

Response to treatment was evaluated according to the following criteria (modified from the National Cancer Institute/Cancer and Leukemia Group B criteria); The best overall response was defined as the best overall response recorded during the time period from the start of the treatment until the end of the treatment period, progression or death (whichever was earlier). Possible categories for best overall response were CR, CRi, Partial remission (PR), no change (NC), Progressive disease (PD) and no assessment. Partial remission (PR). All of the criteria for CR had to be met, except that the bone marrow had to contain ≥ 5% but less than 25% blasts (or ≤ 50% of initial blast count), or < 5% blasts in the presence of Auer rods or abnormal morphology. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: participants	0	0	0	0	0	0	0	1	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Event free survival (EFS)

Top of page

End point title

Event free survival (EFS)

End point description

EFS was defined as the duration of time from randomisation to time of treatment failure (i.e. PD), relapse from CR, or death from any cause, whichever came first. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: days
arithmetic mean (standard deviation)	35 ( 15.6 )	122.3 ( 120 )	32 ( 1 )	117.5 ( 102.4 )	60.4 ( 52.6 )	62 ( 54.1 )	209 ( 315.8 )	65 ( 41.5 )	168.8 ( 219.3 )	62.7 ( 53.9 )	138.7 ( 183.2 )	48.5 ( 36.9 )	174 ( 67.2 )	30 ( 7.3 )

No statistical analyses for this end point

Secondary: Relapse free survival

Top of page

End point title

Relapse free survival

End point description

Relapse-free survival was defined only for patients who achieved CR/CRi and was measured from the date of attaining CR/CRi until the date of recurrence or death from any cause, whichever occurred first. Number of patients having relapse free survival are presented. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Number of subjects analysed

0 ^[4]

0 ^[5]

0 ^[6]

0 ^[7]

0 ^[8]

0 ^[9]

0 ^[10]

Units: participants

Notes
[4] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[5] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[6] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[7] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[8] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[9] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint
[10] - No patients in this treatment arm had CR/CRi to qualify for evaluation of this endpoint

No statistical analyses for this end point

Secondary: Remission duration

Top of page

End point title

Remission duration

End point description

Remission duration analysis was defined only for patients who achieved CR, and was measured from the date of attaining CR until the date of disease recurrence (relapse). For patients who died without report of relapse, remission duration was censored on the date of death, regardless of the cause. Only patients included in treated set with observed cases values were considered for evaluation. 99999: As only one participant is analysed, SD is not calculable

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	0 ^[11]	0 ^[12]	0 ^[13]	1	0 ^[14]	1	1	0 ^[15]	1	0 ^[16]	1	0 ^[17]	1	0 ^[18]
Units: days
arithmetic mean (standard deviation)	( )	( )	( )	263 ( 99999 )	( )	28 ( 99999 )	337 ( 99999 )	( )	455 ( 99999 )	( )	128 ( 99999 )	( )	15 ( 99999 )	( )

Notes
[11] - No patients in this treatment arm had observed cases values
[12] - No patients in this treatment arm had observed cases values
[13] - No patients in this treatment arm had observed cases values
[14] - No patients in this treatment arm had observed cases values
[15] - No patients in this treatment arm had observed cases values
[16] - No patients in this treatment arm had observed cases values
[17] - No patients in this treatment arm had observed cases values
[18] - No patients in this treatment arm had observed cases values

No statistical analyses for this end point

Secondary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point description

OS was defined for all patients that entered the trial, and measured from the date of randomization until death from any cause. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

Data collected up to cut-off date 20 Oct 2011, Up to 1239 days

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	4	3	6
Units: days
arithmetic mean (standard deviation)	122.8 ( 166.2 )	212 ( 55.1 )	71.3 ( 40.5 )	236.8 ( 225.5 )	148.7 ( 125.5 )	86.6 ( 58.1 )	236.8 ( 322.9 )	137.3 ( 121.7 )	198.2 ( 260.1 )	339.7 ( 364.8 )	175.7 ( 175.4 )	73 ( 31.3 )	294.7 ( 101.5 )	48.7 ( 17.9 )

No statistical analyses for this end point

Secondary: Cmax (maximum measured concentration of BI 811283 in plasma)

Top of page

End point title

Cmax (maximum measured concentration of BI 811283 in plasma)

End point description

Cmax (maximum measured concentration of BI 811283 in plasma) during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	3	3	6
Units: nmol/L
geometric mean (geometric coefficient of variation)	8.03 ( 32.3 )	64.1 ( 686 )	104 ( 321 )	153 ( 108 )	214 ( 38.8 )	272 ( 30 )	7.06 ( 10 )	66.1 ( 85.3 )	139 ( 33.8 )	499 ( 101 )	445 ( 71 )	631 ( 31 )	528 ( 40.5 )	1130 ( 53.3 )

No statistical analyses for this end point

Secondary: AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity)

Top of page

End point title

AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity)

End point description

AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) during Cycle 1. Treated set (Only patients with observed cases (OC) values were analysed).

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	2	3	6	7	4	4	5	3	7	3	3	6
Units: nmol·h/L
geometric mean (geometric coefficient of variation)	177 ( 28.2 )	985 ( 311 )	1000 ( 40.7 )	2790 ( 130 )	4400 ( 62.9 )	5620 ( 27.9 )	192 ( 47.7 )	1490 ( 98.1 )	2840 ( 29.6 )	8870 ( 59.9 )	9770 ( 63 )	14100 ( 32.6 )	12800 ( 64.3 )	23200 ( 57.9 )

No statistical analyses for this end point

Secondary: AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point)

Top of page

End point title

AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point)

End point description

AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	7	7	4	4	5	3	7	3	3	6
Units: nmol·h/L
geometric mean (geometric coefficient of variation)	169 ( 30.5 )	939 ( 328 )	2010 ( 207 )	2350 ( 105 )	2810 ( 135 )	5340 ( 27.2 )	156 ( 17.5 )	1450 ( 97.3 )	2730 ( 29.1 )	8680 ( 60.4 )	9260 ( 63.6 )	13700 ( 31.7 )	12100 ( 63.1 )	21700 ( 55.2 )

No statistical analyses for this end point

Secondary: Cmax,ss (maximum measured concentration of BI 811283 in plasma at steady state)

Top of page

End point title

Cmax,ss (maximum measured concentration of BI 811283 in plasma at steady state) ^[19]

End point description

Cmax (maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation. Steady state analyses is not applicable for Treatment schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment schedule B.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

Notes
[19] - 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: Only those arms for which the statistics are presented in the clinical trial report thus, those that would yield meaningful results were reported.

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A
Number of subjects analysed	3	3	3	3	7	7
Units: nmol/L
geometric mean (geometric coefficient of variation)	8.02 ( 4.59 )	24.7 ( 18.5 )	43.3 ( 5.58 )	141 ( 52.2 )	213 ( 96.1 )	229 ( 67.9 )

No statistical analyses for this end point

Secondary: AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state

Top of page

End point title

AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state ^[20]

End point description

AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation.Steady state analyses is not applicable for Treatment schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment schedule B. 99999: Not calculated as estimates of summary statistical values are not considered reliable if data from fever than 2/3 of tested subjects are available, according to Boehringer-Ingelheim Clinical PK SOP.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

Notes
[20] - 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: Only those arms for which the statistics are presented in the clinical trial report thus, those that would yield meaningful results were reported.

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A
Number of subjects analysed	3	3	1	3	6	7
Units: nmol·h/L
geometric mean (geometric coefficient of variation)	188 ( 12.7 )	615 ( 15.3 )	99999 ( 99999 )	4460 ( 41.8 )	5140 ( 105 )	4750 ( 58.1 )

No statistical analyses for this end point

Secondary: AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state

Top of page

End point title

AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state ^[21]

End point description

AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation. Steady state analyses is not applicable for Treatment schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment schedule B.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

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: Only those arms for which the statistics are presented in the clinical trial report thus, those that would yield meaningful results were reported.

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A
Number of subjects analysed	3	3	3	3	7	7
Units: nmol·h/L
geometric mean (geometric coefficient of variation)	183 ( 14.3 )	597 ( 15 )	1620 ( 58.2 )	4330 ( 40.5 )	4340 ( 83.6 )	4820 ( 55.6 )

No statistical analyses for this end point

Secondary: tmax (time from dosing to maximum measured concentration of BI 811283 in plasma)

Top of page

End point title

tmax (time from dosing to maximum measured concentration of BI 811283 in plasma)

End point description

tmax (time from dosing to maximum measured concentration of BI 811283 in plasma) during Cycle 1. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Number of subjects analysed

Units: hours

median (full range (min-max))

24 (6 to 24.1)

26 (6 to 48)

25 (24 to 32)

22.7 (6 to 24.1)

6 (4.1 to 24.3)

23.6 (5.9 to 24.5)

23.9 (4 to 24.2)

6 (6 to 6)

24.1 (6 to 26.8)

24.9 (23.6 to 32)

6 (6 to 25)

23.9 (23.9 to 24.1)

5.9 (4.8 to 6)

14.8 (3.9 to 26.1)

No statistical analyses for this end point

Secondary: tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state)

Top of page

End point title

tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) ^[22]

End point description

tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state) during Cycle 1 Only patients included in treated set with observed cases values were considered for evaluation. Steady state analyses is not applicable for Treatment schedule B, since pharmacokinetic analyses was performed after a single dose for Treatment schedule B.

End point type

Secondary

End point timeframe

-0.05 hours before and 1:00, 4:00, 6:00, 24:00, 25:00, 26:00, 28:00, 32:00, 36:00, 48:00 hours after administration of BI 811283

Notes
[22] - 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: Only those arms for which the statistics are presented in the clinical trial report thus, those that would yield meaningful results were reported.

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A
Number of subjects analysed	3	3	3	3	7	7
Units: hours
median (full range (min-max))	23.9 (4.1 to 23.9)	24 (4 to 24)	6 (4 to 24)	6 (4.1 to 24)	6 (5.9 to 23.5)	6 (4 to 23.8)

No statistical analyses for this end point

Secondary: Cmax (maximum measured concentration of Cytarabine in plasma)

Top of page

End point title

Cmax (maximum measured concentration of Cytarabine in plasma)

End point description

Cmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	6	7	4	3	5	3	7	3	3	6
Units: ng/mL
geometric mean (geometric coefficient of variation)	53.2 ( 65.4 )	72.6 ( 31 )	49 ( 80.6 )	64.9 ( 49.5 )	61.9 ( 57.3 )	46 ( 54.1 )	46.3 ( 31.8 )	49.8 ( 58.1 )	55 ( 16.5 )	65.1 ( 44.5 )	49.4 ( 58.9 )	48.6 ( 88.4 )	49 ( 77 )	68.7 ( 33.1 )

No statistical analyses for this end point

Secondary: Tmax (time from dosing to maximum measured concentration of Cytarabine in plasma)

Top of page

End point title

Tmax (time from dosing to maximum measured concentration of Cytarabine in plasma)

End point description

Tmax of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283. Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Number of subjects analysed

Units: hours

median (full range (min-max))

0.5 (0.5 to 1)

0.92 (0.5 to 1)

0.83 (0.5 to 1.4)

0.48 (0.42 to 0.53)

0.55 (0.5 to 1.5)

0.5 (0.4 to 0.7)

0.5 (0.5 to 0.5)

0.58 (0.47 to 1)

0.5 (0.43 to 0.67)

0.5 (0.45 to 1)

0.5 (0.47 to 0.5)

0.48 (0.48 to 1)

0.49 (0.48 to 0.57)

No statistical analyses for this end point

Secondary: AUC (0-inf) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 extrapolated to infinity)

Top of page

End point title

AUC (0-inf) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 extrapolated to infinity)

End point description

AUC (0-inf) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283. Only patients included in treated set with observed cases values were considered for evaluation. 99999: Not calculated as estimates of summary statistical values are not considered reliable if data from fever than 2/3 of tested subjects are available, according to Boehringer-Ingelheim Clinical PK SOP.

End point type

Secondary

End point timeframe

-0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	2	3	3	4	5	4	2	3	3	7	3	2	5
Units: ng·h/mL
geometric mean (geometric coefficient of variation)	104 ( 31.4 )	122 ( 6.89 )	102 ( 31.5 )	85.4 ( 35.3 )	65.9 ( 42.5 )	68.1 ( 41.4 )	62 ( 24.1 )	99999 ( 99999 )	99999 ( 99999 )	71.2 ( 20.7 )	72.7 ( 23.6 )	75.5 ( 27.2 )	76.9 ( 19.5 )	76.8 ( 42.6 )

No statistical analyses for this end point

Secondary: AUC (0-tz) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 to the time of the last quantifiable data point)

Top of page

End point title

AUC (0-tz) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 to the time of the last quantifiable data point)

End point description

AUC (0-tz) of Cytarabine after a 20 mg Subcutaneous Dose on the First Day of BI 811283 Only patients included in treated set with observed cases values were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05 hours before and 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours after administration of Cytarabine

End point values	5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	15mg BI 811283 +20mg Cytarabine - Treatment Schedule A	30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A	60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A	5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B	240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B	420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B
Number of subjects analysed	4	3	3	4	6	7	4	3	5	3	7	3	3	6
Units: ng·h/L
geometric mean (geometric coefficient of variation)	45 ( 156 )	66.9 ( 73.8 )	66.8 ( 57.6 )	71.8 ( 26.4 )	46.6 ( 51.2 )	42.3 ( 64.3 )	45.9 ( 20 )	33.9 ( 245 )	57 ( 18.2 )	60.2 ( 30.4 )	52.5 ( 38.8 )	52.1 ( 42.1 )	41.3 ( 87.2 )	51.6 ( 38.1 )

No statistical analyses for this end point

Secondary: Pharmacodynamic Monitoring

Top of page

End point title

Pharmacodynamic Monitoring

End point description

Pharmacodynamic monitoring: drug effect on leukaemia cells (e.g. polyploidy, histone H3 phosphorylation, morphologic changes). An evaluation of this secondary endpoint is not possible due to missing samples/ samples of poor quality of the provided material. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

On Day 5, i.e. 72 hours after the end of the first BI 811283 infusion, and on Day 28 in the first cycle only

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Number of subjects analysed

0 ^[23]

0 ^[24]

0 ^[25]

0 ^[26]

0 ^[27]

0 ^[28]

0 ^[29]

0 ^[30]

0 ^[31]

0 ^[32]

0 ^[33]

0 ^[34]

0 ^[35]

0 ^[36]

Units: NA

number (not applicable)

Notes
[23] - Due to the premature termination of the trial, no subjects were analysed
[24] - Due to the premature termination of the trial, no subjects were analysed
[25] - Due to the premature termination of the trial, no subjects were analysed
[26] - Due to the premature termination of the trial, no subjects were analysed
[27] - Due to the premature termination of the trial, no subjects were analysed
[28] - Due to the premature termination of the trial, no subjects were analysed
[29] - Due to the premature termination of the trial, no subjects were analysed
[30] - Due to the premature termination of the trial, no subjects were analysed
[31] - Due to the premature termination of the trial, no subjects were analysed
[32] - Due to the premature termination of the trial, no subjects were analysed
[33] - Due to the premature termination of the trial, no subjects were analysed
[34] - Due to the premature termination of the trial, no subjects were analysed
[35] - Due to the premature termination of the trial, no subjects were analysed
[36] - Due to the premature termination of the trial, no subjects were analysed

No statistical analyses for this end point

Secondary: Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone

Top of page

End point title

Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone

End point description

The study protocol originally included a phase II part with a treatment arm in which Cytarabine was given alone, however the sponsor discontinued the clinical development of BI 811283, therefore the protocol was amended and the reference therapy arm was removed from the study protocol" -> (Protocol Amendment 5, version 19 -May-2010, approved 28-Jun-2010). Since there was never a treatment arm in which Cytarabine was given alone; hence pharmacokinetics are not calculated. Only patients included in treated set (TS) were considered for evaluation.

End point type

Secondary

End point timeframe

-0.05, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 hours

5mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

15mg BI 811283 +20mg Cytarabine - Treatment Schedule A

30mg BI 811283+ 20mg Cytarabine- Treatment Schedule A

60mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

100mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

120mg BI 811283+ 20mg Cytarabine - Treatment Schedule A

5mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

40mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

80mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

160mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

240mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

300mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

360mg BI 811283+ 20mg Cytarabine - Treatment Schedule B

420mg BI 811283+ 20mg Cytarabine- Treatment Schedule B

Number of subjects analysed

0 ^[37]

0 ^[38]

0 ^[39]

0 ^[40]

0 ^[41]

0 ^[42]

0 ^[43]

0 ^[44]

0 ^[45]

0 ^[46]

0 ^[47]

0 ^[48]

0 ^[49]

0 ^[50]

Units: NA

number (not applicable)

Notes
[37] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[38] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[39] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[40] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[41] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[42] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[43] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[44] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[45] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[46] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[47] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[48] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[49] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.
[50] - There was never a treatment arm in which Cytarabine was given alone, thus no subjects were analysed.

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Data from first treatment administration until cut-off date of 20 October 2011; up to 1239 days

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

5mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

15mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

30mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

60mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

100mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

120mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

Reporting group description

Reporting group title

5mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

40mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

80mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

160mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

240mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

300mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

360mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

Reporting group title

420mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Reporting group description

5mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

15mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

30mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

60mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

100mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

120mg BI 811283 + 20mg Cytarabine - Treatment Schedule A

5mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

40mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

80mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

160mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

240mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

300mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

360mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

420mg BI 811283 + 20mg Cytarabine - Treatment Schedule B

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 4 (75.00%)

2 / 3 (66.67%)

3 / 3 (100.00%)

4 / 4 (100.00%)

6 / 7 (85.71%)

4 / 4 (100.00%)

3 / 4 (75.00%)

5 / 5 (100.00%)

3 / 3 (100.00%)

7 / 7 (100.00%)

3 / 4 (75.00%)

3 / 3 (100.00%)

5 / 6 (83.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Malignant neoplasm progression

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

1 / 4 (25.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

2 / 6 (33.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

Vascular disorders

Hypotension

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Asthenia

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Death

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

2 / 7 (28.57%)

0 / 4 (0.00%)

1 / 5 (20.00%)

2 / 3 (66.67%)

3 / 7 (42.86%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

0 / 1

0 / 2

0 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Multi-organ failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

2 / 4 (50.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

0 / 1

0 / 0

0 / 1

0 / 0

Pyrexia

subjects affected / exposed

1 / 4 (25.00%)

2 / 3 (66.67%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

2 / 4 (50.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

1 / 3

0 / 0

1 / 1

0 / 0

2 / 3

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Epistaxis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lung infiltration

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 6 (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

0 / 1

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood uric acid increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

C-reactive protein increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

1 / 5 (20.00%)

2 / 3 (66.67%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 3

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transaminases increased

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural haematoma

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urostomy complication

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Aplasia

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac failure

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Cardiac fibrillation

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Cerebral haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebral ischaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Convulsion

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dizziness

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Disseminated intravascular coagulation

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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 / 4 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

2 / 4 (50.00%)

2 / 7 (28.57%)

0 / 7 (0.00%)

3 / 4 (75.00%)

1 / 4 (25.00%)

1 / 5 (20.00%)

1 / 3 (33.33%)

2 / 7 (28.57%)

2 / 4 (50.00%)

2 / 3 (66.67%)

2 / 6 (33.33%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 3

0 / 2

0 / 0

1 / 3

1 / 2

2 / 2

0 / 1

0 / 4

1 / 3

0 / 2

deaths causally related to treatment / all

0 / 0

Leukocytosis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Eye disorders

Eye haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Diarrhoea

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Rectal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Cholecystitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Renal failure

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal failure acute

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abscess

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Arthritis infective

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bacterial sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Cellulitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Clostridium difficile infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Diverticulitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocarditis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Folliculitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gingivitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Groin abscess

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haematoma infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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 / 4 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Neutropenic sepsis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Osteomyelitis

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

2 / 4 (50.00%)

0 / 3 (0.00%)

2 / 4 (50.00%)

2 / 7 (28.57%)

1 / 7 (14.29%)

1 / 4 (25.00%)

2 / 4 (50.00%)

2 / 5 (40.00%)

0 / 3 (0.00%)

2 / 7 (28.57%)

0 / 4 (0.00%)

1 / 3 (33.33%)

1 / 6 (16.67%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 2

0 / 1

0 / 2

1 / 2

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Pneumonia fungal

subjects affected / exposed

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

1 / 7 (14.29%)

2 / 4 (50.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

Skin infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 4 (25.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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 / 4 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 4 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (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

Tooth infection

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 6 (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

Hyperuricaemia

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour lysis syndrome

subjects affected / exposed

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Fasciitis

subjects affected / exposed

1 / 4 (25.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	5mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	15mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	30mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	60mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	100mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	120mg BI 811283 + 20mg Cytarabine - Treatment Schedule A	5mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	40mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	80mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	160mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	240mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	300mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	360mg BI 811283 + 20mg Cytarabine - Treatment Schedule B	420mg BI 811283 + 20mg Cytarabine - Treatment Schedule B
Total subjects affected by non serious adverse events
subjects affected / exposed	4 / 4 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	4 / 4 (100.00%)	7 / 7 (100.00%)	7 / 7 (100.00%)	4 / 4 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	3 / 3 (100.00%)	6 / 7 (85.71%)	4 / 4 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Osteoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Metastases to bone
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vascular disorders
Circulatory collapse
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Flushing
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Haematoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 4 (75.00%)	2 / 7 (28.57%)	2 / 7 (28.57%)	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	2 / 4 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	3	2	2	2	0	3	2	2	2	0	1
Hypertension
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hypertensive crisis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Hot flush
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	1	0	0
Hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	1	0	1	1	0	0	0	0	0	0
Intra-abdominal haematoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	2	0	0	0	0	0
Lymphoedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Jugular vein thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Phlebitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	1	0	0	0	0	0
Thrombophlebitis
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	1	0	0	2	0	2	1	2	1	0	2	0	1
Orthostatic hypotension
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Thrombosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vasculitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Surgical and medical procedures
Central venous catheterisation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	1	0	0	0
Catheterisation venous
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	2	0	0	0	0
Asthenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	3	1	0	0	0
Catheter site erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Catheter site inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Catheter site haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Catheter site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	1	0	0	0	0
Chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	0	1	0	0	0	4	0	0	0	2
Chills
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 4 (75.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	1	1	0	2	3	0	0	0	0
Discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Facial pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Feeling cold
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Fatigue
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	1 / 4 (25.00%)	3 / 7 (42.86%)	2 / 7 (28.57%)	1 / 4 (25.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	3 / 3 (100.00%)	4 / 7 (57.14%)	2 / 4 (50.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	0	1	2	2	3	2	2	2	5	9	4	3	1	2
General physical health deterioration
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	4 / 7 (57.14%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	1 / 4 (25.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)
occurrences all number	1	0	0	0	4	6	0	0	0	1	4	1	1	3
Gait disturbance
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	1	0	0	0	0
Inflammation
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Injection site inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Injection site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Injection site reaction
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	3	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Local swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	1	1	0	2	0	0	0	0	0
Mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	1 / 4 (25.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	3 / 7 (42.86%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	2	0	0	0	1	0	0	2	0	3	1	0	1
Oedema
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 4 (50.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	1	1	0	0	3	1	3	0	0	0	0	1
Oedema peripheral
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	2 / 7 (28.57%)	0 / 4 (0.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	3	1	0	0	3	3	3	0	5	0
Pyrexia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	3 / 7 (42.86%)	3 / 7 (42.86%)	2 / 4 (50.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)	3 / 3 (100.00%)	4 / 7 (57.14%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	3	4	5	2	6	4	7	1	4	2
Pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 4 (75.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	1	0	0	4	0	0	0	0	1	0	0	1	1	2
Vessel puncture site pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Social circumstances
Bedridden
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vaginal inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Bronchial secretion retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dysphonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cough
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 4 (50.00%)	2 / 7 (28.57%)	3 / 7 (42.86%)	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	0	1	0	4	2	4	0	1	3	3	0	0	2	2
Epistaxis
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	4 / 7 (57.14%)	0 / 4 (0.00%)	2 / 3 (66.67%)	3 / 6 (50.00%)
occurrences all number	1	1	0	0	1	3	8	0	1	2	6	0	2	3
Dyspnoea
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 4 (0.00%)	2 / 7 (28.57%)	4 / 7 (57.14%)	1 / 4 (25.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	3 / 3 (100.00%)	5 / 7 (71.43%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	2	3	0	3	7	1	3	1	6	5	0	0	4
Hiccups
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	1	0	1	0	0	0	0	0	1
Haemothorax
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Increased upper airway secretion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Lung infiltration
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Lung disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Obstructive airways disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pharyngeal erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	1	0	0	0	0	1	2	0	0	0
Pharyngeal oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pleural effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 7 (28.57%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	2	0	1	1	1	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0
Pulmonary mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pulmonary oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0
Respiratory acidosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Rales
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0
Rhonchi
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0	0	0	0	0	0	0
Stridor
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Respiratory failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Tachypnoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	1	0	0	1
Agitation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Confusional state
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	1	0	0	1	1	1	0	0	0	0
Depression
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Catatonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Disorientation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	1	0	0	0
Hallucination
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	2	0	0	1
Insomnia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	2
Illusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Panic attack
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Mood altered
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	1	0	0	1	1	0	1	0	1	0	0	0
Restlessness
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	1	1	0	0	0	0
Psychotic disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Investigations
Activated partial thromboplastin time
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Alanine aminotransferase decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	6	0	0	0	0	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	5	0	1	0	0	0	0	0
Antithrombin III decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	3	1
Amylase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Aspartate aminotransferase decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	2	1
Basophil count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	0	2	0	1	2	0	0	0	0	5
Blood calcium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	3 / 7 (42.86%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	11	1	0	0	3	3	0	1	4	2
Blood chloride increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Blood chloride decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Blood calcium increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Blood cholinesterase decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood cholesterol increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Blood creatinine decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	2	3	0	0	6	0	1	0	1	2
Blood glucose increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Blood fibrinogen increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Blood magnesium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)
occurrences all number	0	0	0	0	2	1	0	0	0	0	0	0	1	4
Blood phosphorus decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	1	2	0	0	2	1	1	1	0	3
Blood phosphorus increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Blood potassium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	5 / 7 (71.43%)	4 / 7 (57.14%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	1 / 4 (25.00%)	3 / 3 (100.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	3	13	8	0	0	0	2	4	2	12	2
Blood potassium increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Blood sodium decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Blood urea increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	2	2	0	0	2	0	0	0	7	4
Blood triglycerides increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Blood uric acid increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	2	1	3	1
Blood urine present
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
C-reactive protein increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	4 / 7 (57.14%)	2 / 7 (28.57%)	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	4 / 7 (57.14%)	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)
occurrences all number	0	0	0	3	4	2	3	0	0	1	7	2	4	1
Eosinophil count increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Fibrin D dimer increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	5	3	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	0	0	0	2	0	0	0	1	1
Heart rate increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Lipase increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Mean cell haemoglobin concentration increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Mean cell volume decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Oxygen saturation decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	2	0	0	0
Protein total decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Prothrombin time prolonged
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	1	0	0	0	1	1	0	0	0	1
Protein total increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Prothrombin time shortened
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Transaminases increased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0	1	0	0	0	1	0
Weight increased
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	1	1	1	0	0	0	0	0	1	0
pH urine decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
Arrhythmia
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Angina pectoris
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0	0	0	0	0
Bradycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	1	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Myocardial ischaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Cardiovascular insufficiency
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Right ventricular failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	1	0	0	1
Supraventricular tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Ventricular tachycardia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Ventricular extrasystoles
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Aphasia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Cerebral ischaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Balance disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Dementia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Convulsion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Dizziness
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	2 / 7 (28.57%)	2 / 7 (28.57%)	1 / 4 (25.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	1	2	1	1	2	2	2	1	5	2	1	0	1	1
Disturbance in attention
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hemiparesis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0
Headache
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	3 / 7 (42.86%)	2 / 4 (50.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	1	0	1	1	0	1	1	1	0	6	2	0	2
Dysgeusia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Hypotonia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Paraesthesia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Syncope
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	2	0
Spinal haematoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	0	0	1	0	1	1	0	0	1
Tremor
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Transient ischaemic attack
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 4 (25.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	1 / 4 (25.00%)	5 / 7 (71.43%)	5 / 7 (71.43%)	1 / 4 (25.00%)	2 / 4 (50.00%)	1 / 5 (20.00%)	3 / 3 (100.00%)	3 / 7 (42.86%)	1 / 4 (25.00%)	3 / 3 (100.00%)	3 / 6 (50.00%)
occurrences all number	1	5	1	5	7	7	2	7	2	8	4	1	3	4
Disseminated intravascular coagulation
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Febrile neutropenia
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	2 / 7 (28.57%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	2	1	2	3	0	1	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	3	3	0	0	1	1	0	1	1	2
Lymph node pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	4 / 7 (57.14%)	5 / 7 (71.43%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	2 / 4 (50.00%)	3 / 3 (100.00%)	2 / 6 (33.33%)
occurrences all number	0	0	1	3	8	8	1	1	3	1	5	3	11	2
Lymphadenopathy
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 4 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 4 (50.00%)	2 / 7 (28.57%)	2 / 7 (28.57%)	2 / 4 (50.00%)	3 / 4 (75.00%)	3 / 5 (60.00%)	2 / 3 (66.67%)	2 / 7 (28.57%)	2 / 4 (50.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)
occurrences all number	0	3	1	4	3	11	5	9	3	7	7	2	5	2
Neutropenia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	3 / 3 (100.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	2	2	0	0	2	1	4	0	8	2
Ear and labyrinth disorders
Cerumen impaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ear haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Tinnitus
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Eye disorders
Cataract
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Eye haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Eye pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Eye pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Eyelid oedema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Eyelid bleeding
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Photopsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	3	1	0	0	0	0	0	0	0	0	0
Abdominal discomfort
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	3 / 4 (75.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	0	0	0	1	2	2	4	0	1	3	4	0	1	1
Abdominal pain lower
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	1	1	1	0	1	0	0	0	1
Anal fissure
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Anal ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Anal haemorrhage
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Aphthous stomatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Colitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Constipation
subjects affected / exposed	1 / 4 (25.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 4 (50.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	1 / 4 (25.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)
occurrences all number	2	2	0	3	1	0	1	0	0	2	0	2	3	0
Diarrhoea
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	3 / 7 (42.86%)	1 / 7 (14.29%)	3 / 4 (75.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 4 (0.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)
occurrences all number	0	0	0	4	5	1	3	4	4	1	3	0	2	2
Dry mouth
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	1	0	0	0	0	0
Faecal incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	1	0
Dyspepsia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	1	0	0
Flatulence
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	1	1	0	0	1	0	0	0
Faecaloma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Gingival pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Gingival bleeding
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	0	0	1	0	0
Gingival swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haematemesis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Haematochezia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	1
Lip ulceration
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Mouth haemorrhage
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	1	0	0	0	0	0
Melaena
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	1	0	0	0
Nausea
subjects affected / exposed	2 / 4 (50.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	2 / 4 (50.00%)	3 / 7 (42.86%)	4 / 7 (57.14%)	1 / 4 (25.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	3 / 4 (75.00%)	3 / 3 (100.00%)	2 / 6 (33.33%)
occurrences all number	2	2	0	4	5	7	1	3	11	7	2	3	4	3
Oral disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Oral mucosal erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Oral pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Palatal disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Parotid gland enlargement
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Periodontal disease
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Rectal tenesmus
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Retching
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Salivary gland pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	1	0	1	0	1	0	0	0	0	0
Tongue coated
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Tongue discolouration
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Toothache
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	2	0	1	0	0	1	0	0
Vomiting
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	4 / 7 (57.14%)	3 / 7 (42.86%)	2 / 4 (50.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	1	0	2	5	7	3	3	5	4	2	1	0	1
Hepatobiliary disorders
Hepatic cyst
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hepatic lesion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hepatic vein occlusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	1 / 4 (25.00%)	2 / 3 (66.67%)	2 / 6 (33.33%)
occurrences all number	0	0	0	1	1	2	0	0	0	1	2	1	2	2
Cold sweat
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Decubitus ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	2	0	1	0
Dermatitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	0
Drug eruption
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1	0	0	0
Eczema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	2	0	0	0	1	0
Erythema nodosum
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Milia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	1	2	1	1	0	2	0	0	1	0	1
Pain of skin
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Palmar erythema
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Night sweats
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 4 (50.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)
occurrences all number	0	4	0	2	2	1	0	2	1	4	0	1	1	2
Papule
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Petechiae
subjects affected / exposed	2 / 4 (50.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	2	1	1	1	2	2	1	1	3	1	0	0	0
Pruritus
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	6	0	3	0	1	0
Psoriasis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	1	0	1	0	0	3	0	0	0
Pruritus generalised
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin hyperpigmentation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Skin lesion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	1	0
Swelling face
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Skin mass
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Renal and urinary disorders
Bladder spasm
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Dysuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Haemoglobinuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	1	1	0	0	0
Incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Micturition urgency
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Micturition disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nocturia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	1	0
Renal disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Renal cyst
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Renal failure acute
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Renal failure
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	2	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 4 (25.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	1	1	1	2	0	1	0	1	3	0	1	1	0
Arthralgia
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	1	0	1	0	0	2	0	0	0	2	1	0	2	0
Bone lesion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Bone pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	1	2	1	0	0
Bursitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Fistula
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Flank pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Fracture pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Joint swelling
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Haemarthrosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	2	1	0	0	0	0	0	0
Mobility decreased
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Muscle disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	2	1	1	0	0	0
Muscular weakness
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0	0	0	0
Myalgia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	2	4	1	0	1	0
Pain in extremity
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	2 / 4 (50.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	2	1	3	1	2	2	1	0	0	1
Pain in jaw
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Spinal osteoarthritis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Spinal pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Tendon pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Infections and infestations
Bacterial disease carrier
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	1	0	1	1	0	0
Bronchiolitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Candida infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Bronchopulmonary aspergillosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Clostridial infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Clostridium difficile infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Device related infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Enterobacter infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Enterococcal infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	1	1	0	0	0	0	0	0
Erysipelas
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Fungal skin infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Infection
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Herpes simplex
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	0	0	0	0	0	0
Localised infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Infectious disease carrier
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Nasopharyngitis
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	0	0	0	0	1	0	0	0	1	1
Oral herpes
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Periodontitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pneumonia
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	1	0	0	0
Pneumonia fungal
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	1	0	0	0
Pseudomonas infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Postoperative wound infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Puncture site infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory tract infection fungal
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	0
Skin infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	1	0	0	0	0	0	0	0	0
Skin candida
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Soft tissue infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Staphylococcal infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0
Urinary tract infection staphylococcal
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	1	0	0	0	0	0	0	1	1	1	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Allergic transfusion reaction
subjects affected / exposed	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	0	0
Bone contusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Excoriation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Drug administration error
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	2	0	2	5	0	0	0	0	0
Fall
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	3 / 3 (100.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)
occurrences all number	0	0	0	4	1	0	1	0	2	3	2	0	1	1
Head injury
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Laceration
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	1	0	0	0
Post procedural haematoma
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lumbar vertebral fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Post procedural inflammation
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Post procedural haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Procedural dizziness
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Procedural pain
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	1	0	0	0
Pubis fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Rib fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Transfusion reaction
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Tracheal haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Traumatic haemorrhage
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Wound
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	2 / 7 (28.57%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0
Wrist fracture
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	1
Decreased appetite
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	4 / 7 (57.14%)	4 / 7 (57.14%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	3 / 7 (42.86%)	0 / 4 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	5	5	2	0	0	5	3	0	0	3
Alkalosis
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dehydration
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	1	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	1	0	0	0	0	0	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	6	0	0	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hypokalaemia
subjects affected / exposed	1 / 4 (25.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 4 (50.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 4 (50.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	1	2	0	0	2	3	7	1	0	1	0	0
Iron overload
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Metabolic disorder
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Tumour lysis syndrome
subjects affected / exposed	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

04 Mar 2008

•More detail was provided on the criteria used to assess patients ineligible for intensive treatment. •Additional procedures (cytogenetics and molecular genetics) were amended to allow for the most up-to-date AML diagnostics. •The time specification 72 hours after BI 811283 treatment was defined more precisely as 72 hours after the end of the first 24 hours continuous infusion of the trial drug. •The instructions for pharmcodynamic sampling were changed to be consistent between the text and the flowcharts. •PK sampling numbers were revised to make the numbering consecutive.

16 Sep 2008

•The dose escalation levels were amended based on data available from trial 1247.1, so that the next cohort started at a dose level proven safe in trial 1247.1. However, since BI 811283 was investigated as monotherapy in trial 1247.1, whereas in this trial BI 811283 is combined with low-dose cytarabine (with overlapping haematological toxicity expected), the BI 811283 dose for the next cohort was approximately half the highest BI 811823 dose that was considered safe in the first cycle of the ongoing monotherapy trial 1247.1. •PK sampling 36 hours after start of administration of the trial drug was changed from mandatory to optional since this sampling occurred at nighttime. •Up to 7 days hydroxyurea treatment for peripheral blast control was allowed, up until 1 day before the first administration of the trial drugs.

11 Feb 2009

•A formal safety analysis after the Phase I part of the trial, and if necessary an updated risk-benefit assessment, was implemented. •To get more comprehensive survival data, the follow-up rules were changed to allow longer follow-up. •Details were added regarding the vial size of cytarabine used in the trial. •Rules for pharmacodynamic investigations were changed so that analysis in Phase IIa of the study was optional. •Planned dates of the trial were adjusted.

21 Dec 2009

•Handling instructions of BI 811283 ready-for-use infusion were adapted based on new analytical data and the need for an adjustment of the infusion concentration. •Photostability testing of the diluted drug product revealed a photosensitivity, so changes were made in the storage conditions. •AE and SAE reporting criteria were modified. •Screening for additional mutations/deregulated expression of genes was added to the planned cytogenetic and molecular genetic testing to allow the most up to date exploratory diagnostics. Sample volume was adapted accordingly. •Wording for replacement of patients was unclear for the Phase II part of the trial so this was clarified. •The address of the coordinating investigator was revised. •Inclusion and exclusion criteria were modified to allow inclusion of patients with relapsed and refractory AML in the Phase I part of the trial.

19 May 2010

•The number of patients in Phase I was adapted because more dose escalation cohorts than previously expected were needed to determine the MTD. •Details on Phase IIa of the study were deleted since BI decided not to develop BI 811283 in a Phase II program. •Trial timelines were adapted. •An additional safety laboratory test was added to Day 2 (after the first administration of BI 811283 and cytarabine) in the first treatment cycle to allow for early detection of laboratory changes after the first administration of the trial drugs. •Further instructions were provided on the allowed timelines for pre-treatment of patients with relapsed/refractory AML. •Details were provided on how many omitted doses of cytarabine were acceptable inthe first cycle without the requirement to replace the patient for correct determination of the MTD. •The trial objective was reduced to determine the MTD for the 2 schedules of BI 811283 in combination with cytarabine. •The investigators´ awareness was raised regarding the potential occurrence of tumour lysis syndrome in connection with cytoreductive treatment, and hence to support early diagnosis and management of tumour lysis syndrome within this trial.

08 Jul 2011

•Due to a strategic decision by BI not to further develop the substance BI 811283 in any indication, and since the dose in Group B has been escalated to twice the MTD in schedule A without any DLTs, further dose escalation in Group B was considered unreasonable. In addition, the following changes were made in the TSAP from that specified in the protocol. These changes were made before database lock: •The TSAP further clarified the definition of best response, with this being defined by best overall response and objective response.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
08 Jul 2011	The enrolment of new subjects to participate in this study was stopped, thus no new subjects were entered in the trial as the sponsor decided to discontinue the clinical development of BI 811283.	-

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

Treatment Arm C defined in the protocol was not implemented, because with protocol amendment(19May10) the study design was changed from a phase I/II to a phase I only, so there was never a treatment arm in which Cytarabine was given alone

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: An open Phase I trial to investigate the maximum tolerated dose, safety, efficacy and pharmacokinetics of BI 811283 in combination with cytarabine in patients with previously untreated or relapsed/refractory acute myeloid leukaemia ineligible for intensive treatment

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: The maximum tolerated dose (MTD) of 2 schedules of BI 811283 in combination with cytarabine.

Primary: The maximum tolerated dose (MTD) of 2 schedules of BI 811283 in combination with cytarabine.

Secondary: Response (complete remission [CR], complete remission with incomplete blood count recovery [CRi])

Secondary: Response (complete remission [CR], complete remission with incomplete blood count recovery [CRi])

Secondary: Incidence and intensity of AEs graded according to CTCAE (version 3.0)

Secondary: Incidence and intensity of AEs graded according to CTCAE (version 3.0)

Secondary: Incidence of dose limiting toxicity (DLT)

Secondary: Incidence of dose limiting toxicity (DLT)

Secondary: Partial Remission

Secondary: Partial Remission

Secondary: Event free survival (EFS)

Secondary: Event free survival (EFS)

Secondary: Relapse free survival

Secondary: Relapse free survival

Secondary: Remission duration

Secondary: Remission duration

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Cmax (maximum measured concentration of BI 811283 in plasma)

Secondary: Cmax (maximum measured concentration of BI 811283 in plasma)

Secondary: AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity)

Secondary: AUC(0-inf) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity)

Secondary: AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point)

Secondary: AUC0-tz (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point)

Secondary: Cmax,ss (maximum measured concentration of BI 811283 in plasma at steady state)

Secondary: Cmax,ss (maximum measured concentration of BI 811283 in plasma at steady state)

Secondary: AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state

Secondary: AUC (0-inf, ss)(area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 extrapolated to infinity) at steady state

Secondary: AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state

Secondary: AUC (0-tz,ss) (area under the concentration-time curve of BI 811283 in plasma over the time interval from 0 to the time of the last quantifiable data point) at steady state

Secondary: tmax (time from dosing to maximum measured concentration of BI 811283 in plasma)

Secondary: tmax (time from dosing to maximum measured concentration of BI 811283 in plasma)

Secondary: tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state)

Secondary: tmax,ss (time from dosing to maximum measured concentration of BI 811283 in plasma at steady state)

Secondary: Cmax (maximum measured concentration of Cytarabine in plasma)

Secondary: Cmax (maximum measured concentration of Cytarabine in plasma)

Secondary: Tmax (time from dosing to maximum measured concentration of Cytarabine in plasma)

Secondary: Tmax (time from dosing to maximum measured concentration of Cytarabine in plasma)

Secondary: AUC (0-inf) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 extrapolated to infinity)

Secondary: AUC (0-inf) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 extrapolated to infinity)

Secondary: AUC (0-tz) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 to the time of the last quantifiable data point)

Secondary: AUC (0-tz) (area under the concentration-time curve of Cytarabine in plasma over the time interval from 0 to the time of the last quantifiable data point)

Secondary: Pharmacodynamic Monitoring

Secondary: Pharmacodynamic Monitoring

Secondary: Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone

Secondary: Pharmacokinetics of Cytarabine After a Single Dose and at Steady State When Given Alone

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An open Phase I trial to investigate the maximum tolerated dose, safety, efficacy and pharmacokinetics of BI 811283 in combination with cytarabine in patients with previously untreated or relapsed/refractory acute myeloid leukaemia ineligible for intensive treatment