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Clinical Trial Results:
An open label, Phase Ia/Ib dose finding study with BI 894999 orally administered once a day in patients with advanced malignancies with repeated administration in patients with clinical benefit

Summary
EudraCT number	2015-001111-12
Trial protocol	BE DE DK
Global end of trial date	23 Nov 2021

Results information
Results version number	v2(current)
This version publication date	30 May 2024
First version publication date	15 Dec 2022
Other versions	v1
Version creation reason

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

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Trial information

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Sponsor protocol code

1367.1

ISRCTN number

US NCT number

NCT02516553

WHO universal trial number (UTN)

Sponsor organisation name

Boehringer Ingelheim

Sponsor organisation address

Binger Strasse 173, Ingelheim am Rhein, Germany, 55216

Public contact

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, clintriage.rdg@boehringer-ingelheim.com

Scientific contact

Boehringer Ingelheim, Call Center, Boehringer Ingelheim, 001 18002430127, 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

31 Jan 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

23 Nov 2021

Global end of trial reached?

Yes

Global end of trial date

23 Nov 2021

Was the trial ended prematurely?

Main objective of the trial

The trial comprised a dose escalation phase (Phase Ia) and an expansion phase (Phase Ib). The main objective of this trial part was to determine the maximum tolerated dose (MTD) of BI 894999 monotherapy in patients with advanced and/or metastatic solid tumours in different dosing schedules in 3- or 4-week cycles (Schedule A with continuous dosing, Schedule B, with intermittent dosing [2 weeks on treatment, 1 week off treatment in 3-week cycles]; Schedule C, with intermittent dosing [a loading dose on first day followed by a maintenance dose for the next 6 days and followed by 1 week off treatment, repeated every 2 weeks in 4-week cycles]).

Protection of trial subjects

Only subjects that met all the 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. If a subject continued to take trial medication, close monitoring was adhered to and all adverse events recorded. Rules were implemented in all trials whereby doses would be reduced if required. Thereafter, if further events were reported, the subject would be withdrawn from the trial. Symptomatic treatment of tumour associated symptoms were allowed throughout.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Jul 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 137

Country: Number of subjects enrolled

France: 42

Country: Number of subjects enrolled

Germany: 19

Country: Number of subjects enrolled

Korea, Republic of: 1

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

United States: 28

Worldwide total number of subjects

231

EEA total number of subjects

202

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)

138

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

This was an open label, Phase Ia/Ib dose finding study with BI 894999 orally administered once a day in patients with advanced malignancies with repeated administration in patients with clinical benefit.

Screening details

For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg . For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Blinding implementation details

This was an open-label trial.

Are arms mutually exclusive

Yes

Phase Ia - Schedule A: 0.2 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 0.2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule A: 0.5 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 0.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule A: 1 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 1 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule A: 1.5 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule A: 2 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule A: 5 mg BI 894999

Arm description

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule A was a continuous daily intake in cycles of 21 days.

Phase Ia - Schedule B: 1.5 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Phase Ia - Schedule B: 2 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Phase Ia - Schedule B: 2.5 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2.5 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 2.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ia - Schedule C: 6/3 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Arm description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Arm description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 1.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Arm description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Arm description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally 2.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Arm description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 4 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 4 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Arm description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)

Arm description

This arm included adult patients diagnosed with small cell lung cancer (SCLC). SCLC patients were initially administered 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days). The Data Monitoring Committee decided on 28 November 2018 to lower the 2.5 mg BI 894999 dose due to safety concerns to 2mg, therefore patients treated before the decision were administered 2.5mg, and patients treated after the decision were administered 2mg.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Some of the patients of this arm were administered orally 2 milligram (mg) of BI 894999. The rest of the patients in this arm were administered 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Arm description

Adult patients diagnosed with colorectal cancer (CRC) were administered orally 2.5 milligram (mg) of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Patients were administered orally 2.5 milligram (mg) of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)

Arm description

This arm included adult patients diagnosed with metastatic castrate resistant prostate cancer (mCRPC). MCRPC patients were initialy administered 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days). The Data Monitoring Committee decided on 28 November 2018 to lower the 2.5 mg BI 894999 dose due to safety concerns to 2mg, therefore patients treated before the decision were administered 2.5mg, and patients treated after the decision were administered 2mg.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Some of the patients of this arm were administered orally 2 milligram (mg) of BI 894999 once daily. The rest of the patients in this arm were administered orally 2.5 mg of BI 894999. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Arm description

Adult patients diagnosed with NUT carcinoma (NC) were administered orally 2.5 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. The 2.5 mg dose could be reduced to 2 mg in case of adverse events.

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)

Arm description

This arm included adult patients diagnosed with NUT carcinoma (NC). The DMC reclaimed the maximum tolerated dose (MTD) as 6/3mg on 08 July 2020 after 1 patient was already treated with 7/3.5mg, so the first patient in NC and all the following patients were treated with 6/3mg. Patients in were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C).

Arm type

Experimental

Investigational medicinal product name

BI 894999

Investigational medicinal product code

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

Some of the patients in this arm were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The rest of the patients in this arm were administered orally once daily on Day 1 of each cycle a loading dose of 7 mg of BI 894999, followed by six days intake of the maintenance dose of 3.5 mg of BI 894999 once daily according to Schedule C.

Number of subjects in period 1 ^[1]	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Started	2	2	3	6	6	2	6	6	13	4	15	12	8	4	2	2	2	12	14	11	20	22
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	2	2	3	6	6	2	6	6	13	4	15	12	8	4	2	2	2	12	14	11	20	22
Dose limiting toxicity (DLTs)	-	-	-	-	3	1	1	-	1	-	-	1	-	1	-	-	1	1	-	2	-	-
Other Adverse Events	-	-	-	1	-	1	-	-	-	1	3	2	-	1	-	-	-	2	1	2	2	1
other reasons than listed	-	-	-	-	-	-	-	1	1	-	1	1	-	-	-	-	-	-	-	-	2	2
Progressive disease	2	2	3	5	3	-	5	5	11	3	10	8	8	2	2	2	1	9	12	7	16	18
Refused to continue trial medication	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-	1	-	-	1

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: Out of 231 enrolled patients only 174 entered the trial.

Baseline characteristics

Top of page

Reporting group title

Phase Ia - Schedule A: 0.2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 0.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2.5 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule C: 6/3 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Reporting group description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)

Reporting group description

Reporting group values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)	Total
Number of subjects	2	2	3	6	6	2	6	6	13	4	15	12	8	4	2	2	2	12	14	11	20	22	174
Age categorical
Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment. For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg. For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	1	0	3	5	3	1	4	4	7	2	10	8	3	0	0	0	0	7	6	2	18	19	103
From 65-84 years	1	2	0	1	3	1	2	2	6	2	5	4	5	2	2	2	1	5	8	9	2	3	68
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0	0	3
Age Continuous
Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment. For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg . For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.
Units: years
arithmetic mean (standard deviation)	63.5 ( 10.6 )	69.5 ( 2.1 )	46.7 ( 9.3 )	57.5 ( 11.9 )	53.5 ( 18.1 )	54.5 ( 26.2 )	60.7 ( 10.8 )	61.5 ( 13.0 )	64.5 ( 7.5 )	63.3 ( 12.8 )	59.7 ( 12.0 )	62.5 ( 6.5 )	71.4 ( 10.9 )	78.8 ( 9.0 )	68.5 ( 2.1 )	68.5 ( 2.1 )	79.0 ( 9.9 )	63.5 ( 7.3 )	66.2 ( 6.3 )	69.7 ( 4.1 )	44.4 ( 13.9 )	40.5 ( 16.5 )	-
Sex: Female, Male
Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment. For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg. For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.
Units: Participants
Female	1	0	2	2	6	0	3	1	4	2	5	7	1	1	1	0	1	5	6	0	5	8	61
Male	1	2	1	4	0	2	3	5	9	2	10	5	7	3	1	2	1	7	8	11	15	14	113
Race (NIH/OMB)
Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment. For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg. For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asian	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	4
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	3
White	2	2	3	6	6	2	6	6	13	4	15	12	2	4	2	1	0	7	9	8	14	16	140
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	6	0	0	1	2	4	5	2	3	4	27
Ethnicity (NIH/OMB)
Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment. For Phase Ib-Schedule B SCLC, Phase Ib-Schedule B mCRPC, DMC lowered the dose of SCLC and mCRPC, thus patients treated prior the decision took 2.5mg BI 894999 and patients treated after the decision received 2mg. For Phase Ib - Schedule C NC, the dose was lowered since DMC reclaimed the MTD as 6/3mg after 1 patient already treated with 7/3.5mg.
Units: Subjects
Hispanic or Latino	0	0	0	0	1	0	0	0	0	0	1	2	0	0	0	0	0	0	1	0	0	1	6
Not Hispanic or Latino	2	2	3	6	5	2	6	6	13	4	14	10	2	4	2	2	1	8	8	9	17	17	143
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0	0	0	6	0	0	0	1	4	5	2	3	4	25

End points

Top of page

Reporting group title

Phase Ia - Schedule A: 0.2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 0.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2.5 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule C: 6/3 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Reporting group description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)

Reporting group description

Subject analysis set title

Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with NUT carcinoma (NC) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. This Subject Analysis Set is reporting descriptive statistics for the endpoints AUC0-24 and Cmax.

Subject analysis set title

Phase Ib - Schedule B: BI 894999 2 mg (solid tumours+NC)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with one of the following cancer types small cell lung cancer (SCLC); metastatic castrate resistant prostate cancer (mCRPC); NUT carcinoma (NC) were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. This Subject Analysis Set is reporting descriptive statistics for the endpoints AUC0-24 and Cmax.

Subject analysis set title

Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with one of the following cancer types small cell lung cancer (SCLC); metastatic castrate resistant prostate cancer (mCRPC); colorectal cancer (CRC); NUT carcinoma (NC) were administered orally 2.5 milligram (mg) of BI 894999, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. This Subject Analysis Set is reporting descriptive statistics for the endpoint AUC0-24.

Subject analysis set title

Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with NUT carcinoma (NC) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). This Subject Analysis Set is reporting descriptive statistics for the endpoint AUC0-24.

Subject analysis set title

Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with NUT carcinoma (NC) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. This subject analysis set is reporting descriptive statistics for the endpoints AUCτ, ss and Cmax, ss.

Subject analysis set title

Phase Ib - Schedule B: 2 mg BI 894999 (NC patients only)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with NUT carcinoma (NC) were administered during the first cycle 2.5 milligram (mg) BI 894999 according to Schedule B and then the dosage was decreased at steady state to 2 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. This subject analysis set is reporting descriptive statistics for the endpoints AUCτ, ss and Cmax, ss.

Subject analysis set title

Phase Ib - Schedule B: BI 894999 2 mg (solid tumours + NC)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with one of the following cancer types small cell lung cancer (SCLC); metastatic castrate resistant prostate cancer (mCRPC); NUT carcinoma (NC) were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. This subject analysis set is reporting descriptive statistics for the endpoints AUCτ, ss and Cmax, ss.

Subject analysis set title

Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with one of the following cancer types small cell lung cancer (SCLC); metastatic castrate resistant prostate cancer (mCRPC); colorectal cancer (CRC); NUT carcinoma (NC) were administered orally 2.5 milligram (mg) of BI 894999, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days. This subject analysis set is reporting descriptive statistics for the endpoints AUCτ, ss and Cmax, ss.

Subject analysis set title

Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)

Subject analysis set type

Per protocol

Subject analysis set description

Adult patients diagnosed with NUT carcinoma (NC) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). This subject analysis set is reporting descriptive statistics for the endpoints AUCτ, ss and Cmax, ss.

Primary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed in the first cycle

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End point title

Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed in the first cycle ^[1] ^[2]

End point description

The following drug related adverse events (AEs) qualified as DLT: - any Common Terminology Criteria for AEs (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: -- inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades -- electrolytes abnormalities that were corrected within 72 hours with treatment - any haematologic AE related to the trial medication defined as follows: -- CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or -- CTCAE grade ≥4 thrombocytopenia, or --CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or -- febrile neutropenia CTCAE grade 3 or higher. - any other drug-related AE preventing the patient from taking his treatment according to given schedule. Maximum Tolerated Dose (MTD) Evaluation Set: Included all patients in the TS of Phase 1a who were not replaced for the MTD determination.

End point type

Primary

End point timeframe

First treatment cycle (the first 21 days for Schedules A and B, the first 28 days for Schedule C).

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: Endpoint was analyzed only descriptively.
[2] - 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: Endpoint was specified only for the participants of the Phase1a.

Phase Ia - Schedule A: 0.2 mg BI 894999

Phase Ia - Schedule A: 0.5 mg BI 894999

Phase Ia - Schedule A: 1 mg BI 894999

Phase Ia - Schedule A: 1.5 mg BI 894999

Phase Ia - Schedule A: 2 mg BI 894999

Phase Ia - Schedule A: 5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999

Phase Ia - Schedule B: 2 mg BI 894999

Phase Ia - Schedule B: 2.5 mg BI 894999

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Phase Ia - Schedule C: 6/3 mg BI 894999

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Number of subjects analysed

2 ^[3]

2 ^[4]

3 ^[5]

6 ^[6]

6 ^[7]

2 ^[8]

5 ^[9]

6 ^[10]

12 ^[11]

3 ^[12]

12 ^[13]

10 ^[14]

8 ^[15]

3 ^[16]

2 ^[17]

2 ^[18]

2 ^[19]

Units: Participants

Notes
[3] - Maximum Tolerated Dose (MTD) Evaluation Set (MTDS)
[4] - MTDS
[5] - MTDS
[6] - MTDS
[7] - MTDS
[8] - MTDS
[9] - MTDS
[10] - MTDS
[11] - MTDS
[12] - MTDS
[13] - MTDS
[14] - MTDS
[15] - MTDS
[16] - MTDS
[17] - MTDS
[18] - MTDS
[19] - MTDS

No statistical analyses for this end point

Primary: Phase Ib: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

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End point title

Phase Ib: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period ^[20] ^[21]

End point description

The following drug related adverse events (AEs) qualified as DLT: - any Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non haematological toxicity considered related to trial medication with the following exceptions: -- inadequately treated nausea, vomiting or diarrhoea. For fatigue, if present at baseline, there had to be an increase of ≥2 grades -- electrolytes abnormalities that were corrected within 72 hours with treatment - any haematologic AE related to the trial medication defined as follows: -- CTCAE grade ≥4 neutropenia lasting ≥ 7 days and/or complicated by infection, or -- CTCAE grade ≥4 thrombocytopenia, or --CTCAE grade≥ 3 thrombocytopenia coupled with grade ≥ 2 of bleeding, or -- febrile neutropenia CTCAE grade 3 or higher. - any other drug-related AE preventing the patient from taking his treatment according to the given schedule. Treated Set in Phase Ib dose expansion (TS PhIb): All patients in the TS who were treated in Phase Ib.

End point type

Primary

End point timeframe

Date of the first administration of study treatment until date of the last administration of study treatment + 30 days residual effect period, up to 883 days.

Notes
[20] - 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: Endpoint was analyzed only descriptively.
[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: Endpoint was specified only for the participants of the Phase 1b.

End point values	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Number of subjects analysed	12 ^[22]	14 ^[23]	11 ^[24]	20 ^[25]	22 ^[26]
Units: Participants	3	2	7	2	3

Notes
[22] - Treated Set (TS) in Phase Ib dose expansion (TS PhIb).
[23] - TS PhIb
[24] - TS PhIb
[25] - TS PhIb
[26] - TS PhIb

No statistical analyses for this end point

Secondary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

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End point title

Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period ^[27]

End point description

End point type

Secondary

End point timeframe

Date of the first administration of study treatment until date of the last administration of study treatment + 30 days residual effect period, up to 463 days.

Notes
[27] - 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: Endpoint was specified only for the participants of the Phase 1a.

Phase Ia - Schedule A: 0.2 mg BI 894999

Phase Ia - Schedule A: 0.5 mg BI 894999

Phase Ia - Schedule A: 1 mg BI 894999

Phase Ia - Schedule A: 1.5 mg BI 894999

Phase Ia - Schedule A: 2 mg BI 894999

Phase Ia - Schedule A: 5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999

Phase Ia - Schedule B: 2 mg BI 894999

Phase Ia - Schedule B: 2.5 mg BI 894999

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Phase Ia - Schedule C: 6/3 mg BI 894999

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Number of subjects analysed

2 ^[28]

2 ^[29]

3 ^[30]

6 ^[31]

6 ^[32]

2 ^[33]

6 ^[34]

6 ^[35]

13 ^[36]

4 ^[37]

15 ^[38]

12 ^[39]

8 ^[40]

4 ^[41]

2 ^[42]

2 ^[43]

2 ^[44]

Units: Participants

Notes
[28] - Treated Set in Phase 1a
[29] - Treated Set in Phase 1a
[30] - Treated Set in Phase 1a
[31] - Treated Set in Phase 1a
[32] - Treated Set in Phase 1a
[33] - Treated Set in Phase 1a
[34] - Treated Set in Phase 1a
[35] - Treated Set in Phase 1a
[36] - Treated Set in Phase 1a
[37] - Treated Set in Phase 1a
[38] - Treated Set in Phase 1a
[39] - Treated Set in Phase 1a
[40] - Treated Set in Phase 1a
[41] - Treated Set in Phase 1a
[42] - Treated Set in Phase 1a
[43] - Treated Set in Phase 1a
[44] - Treated Set in Phase 1a

No statistical analyses for this end point

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma over the time interval from 0 to 24 hours after administration of the first dose (AUC0-24)

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End point title

Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma over the time interval from 0 to 24 hours after administration of the first dose (AUC0-24) ^[45]

End point description

Area under the concentration-time curve of BI 894999 in plasma over the time interval from 0 to 24 hours after administration of the first dose (AUC0-24) for Phase Ia and Phase Ib is reported. 999999=NA- Could not be calculated due to low number of participants with valid AUC0-24 values. Pharmacokinetic (PK) analysis Set (PKS): Included all patients in the treated set (TS) who have at least one evaluable PK parameters. Only participants with evaluable results for this PK parameter are reported.

End point type

Secondary

End point timeframe

5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h and 23h55min after administration of first BI 894999 dose on Day 1 of Cycle 1.

Notes
[45] - 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: In phase Ib, solid tumor patients (SCLC, mCRPC, CRC and NC) are combined by dose level (2 or 2.5mg) as data of all solid tumor patients were needed since no differences were expected, but the NC patients alone were differentiated in an additional subgroup as it was the initial indication for BI 894999.

End point values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)	Phase Ib - Schedule B: BI 894999 2 mg (solid tumours+NC)	Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)	Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)
Number of subjects analysed	2	2	3	5	4	0 ^[46]	3	4	11	4	15	12	7	4	2	2	0 ^[47]	17	1	9	42	2
Units: nanomole * hour /Liter (nmol*h/L)
geometric mean (geometric coefficient of variation)	4.36 ( 21.1 )	6.43 ( 2.78 )	20.5 ( 16.8 )	34.0 ( 69.4 )	64.9 ( 71.0 )	( )	27.7 ( 81.5 )	44.8 ( 34.8 )	51.5 ( 41.7 )	123 ( 37.6 )	212 ( 45.5 )	230 ( 27.3 )	31.7 ( 33.4 )	48.0 ( 26.9 )	53.3 ( 6.91 )	138 ( 7.52 )	( )	56.9 ( 58.6 )	999999 ( 999999 )	39.2 ( 38.8 )	67.6 ( 50.9 )	214 ( 6.01 )

Notes
[46] - No subjects in this arm were analyzed for this endpoint.
[47] - No subjects in this arm were analyzed for this endpoint.

No statistical analyses for this end point

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma after the first dose (Cmax)

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End point title

Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma after the first dose (Cmax) ^[48]

End point description

Maximum measured concentration of BI 894999 in plasma after the first dose (Cmax) for Phase 1a and Phase 1b is reported. 999999=NA- Cmax could not be provided to reduce the risk of patient re-identificaton. Pharmacokinetic (PK) analysis Set (PKS): Included all patients in the treated set (TS) who have at least one evaluable PK parameters. Only participants with evaluable results for this PK parameter are reported.

End point type

Secondary

End point timeframe

5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h and 23h55min after administration of first BI 894999 dose on Day 1 of Cycle 1.

Notes
[48] - 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: In phase Ib, solid tumor patients (SCLC, mCRPC, CRC and NC) are combined by dose level (2 or 2.5mg) as data of all solid tumor patients were needed since no differences were expected, but the NC patients alone were differentiated in an additional subgroup as it was the initial indication for BI 894999.

End point values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)	Phase Ib - Schedule B: BI 894999 2 mg (solid tumours+NC)	Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)	Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)
Number of subjects analysed	2	2	3	5	4	2	3	4	11	4	15	12	7	4	2	2	1	17	1	9	44	15
Units: nanomole/L (nmol/L)
geometric mean (geometric coefficient of variation)	0.393 ( 35.6 )	0.569 ( 46.2 )	1.75 ( 31.6 )	3.79 ( 84.0 )	7.39 ( 56.0 )	16.2 ( 68.0 )	3.00 ( 155 )	3.93 ( 50.2 )	4.48 ( 46.6 )	12.0 ( 85.1 )	19.4 ( 58.4 )	21.0 ( 48.3 )	2.98 ( 34.9 )	4.49 ( 36.0 )	4.75 ( 0.595 )	13.9 ( 12.8 )	999999 ( 999999 )	4.88 ( 50.1 )	999999 ( 999999 )	4.10 ( 37.8 )	6.01 ( 59.6 )	18.8 ( 55.8 )

No statistical analyses for this end point

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma at steady state over a uniform dosing interval τ (AUCτ, ss)

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End point title

Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma at steady state over a uniform dosing interval τ (AUCτ, ss) ^[49]

End point description

Area under the concentration-time curve of BI 894999 in plasma at steady state over a uniform dosing interval τ (AUCτ, ss) for Phase Ia and Ib is reported. The dosing interval is 24 hours (h) for all dose groups. 999999=NA-AUCτ, ss could not be provided to reduce the risk of patient re-identification. Pharmacokinetic (PK) analysis Set (PKS): Included all patients in the treated set (TS) who have at least one evaluable PK parameters. Only participants with evaluable results for this PK parameter are reported.

End point type

Secondary

End point timeframe

5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, and at 23h55min (Schedule A) or 24h (Schedule B & C) following administration on day 14 (Schedule A & B) or day 21 (Schedule C).

Notes
[49] - 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: In phase Ib, solid tumor patients (SCLC, mCRPC, CRC and NC) are combined by dose level (2 or 2.5mg) as data of all solid tumor patients were needed since no differences were expected, but the NC patients alone were differentiated in an additional subgroup as it was the initial indication for BI 894999.

End point values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)	Phase Ib - Schedule B: 2 mg BI 894999 (NC patients only)	Phase Ib - Schedule B: BI 894999 2 mg (solid tumours + NC)	Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)	Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)
Number of subjects analysed	2	2	3	4	4	1	4	6	11	3	14	5	6	3	1	1	1	14	0 ^[50]	1	10	33	11
Units: nanomole hour/Liter (nmolh/)L
geometric mean (geometric coefficient of variation)	10.3 ( 72.6 )	17.9 ( 46.4 )	54.6 ( 40.4 )	76.4 ( 26.6 )	119 ( 90.3 )	999999 ( 999999 )	62.6 ( 49.2 )	81.1 ( 32.1 )	87.0 ( 28.3 )	144 ( 46.4 )	176 ( 37.0 )	226 ( 63.2 )	70.3 ( 38.5 )	120 ( 19.6 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	94.9 ( 43.9 )	( )	999999 ( 999999 )	73.6 ( 58.2 )	125 ( 50.4 )	149 ( 56.7 )

Notes
[50] - No subjects in this arm were analyzed for this endpoint.

No statistical analyses for this end point

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma at steady state over a uniform dosing interval τ (Cmax, ss)

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End point title

Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma at steady state over a uniform dosing interval τ (Cmax, ss) ^[51]

End point description

Maximum measured concentration of BI 894999 in plasma at steady state over a uniform dosing interval τ (Cmax, ss) for Phase Ia and Phase Ib is reported. The dosing interval is 24 hours (h) for all dose groups. 999999=NA-Cmax, ss could not be provided to reduce the risk of patient re-identification. Pharmacokinetic (PK) analysis Set (PKS): Included all patients in the treated set (TS) who have at least one evaluable PK parameters. Only participants with evaluable results for this PK parameter are reported.

End point type

Secondary

End point timeframe

5 minutes (min) before and at 30 min, 1 hour (h), 2h, 3h, 4h, 6h, 8h, and at 23h55min (Schedule A) or 24h (Schedule B & C) following administration on day 14 (Schedule A & B) or day 21 (Schedule C).

Notes
[51] - 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: In phase Ib, solid tumor patients (SCLC, mCRPC, CRC and NC) are combined by dose level (2 or 2.5mg) as data of all solid tumor patients were needed since no differences were expected, but the NC patients alone were differentiated in an additional subgroup as it was the initial indication for BI 894999.

End point values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)	Phase Ib - Schedule B: 2 mg BI 894999 (NC patients only)	Phase Ib - Schedule B: BI 894999 2 mg (solid tumours + NC)	Phase Ib - Schedule B: BI 894999 2.5 mg (solid tumours + NC)	Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)
Number of subjects analysed	2	2	3	6	6	1	4	6	11	3	14	5	6	3	1	1	1	14	0 ^[52]	1	10	33	11
Units: nanomole/Liter (nmol/L)
geometric mean (geometric coefficient of variation)	0.697 ( 59.8 )	1.26 ( 24.9 )	4.06 ( 61.7 )	5.25 ( 60.1 )	11.6 ( 54.4 )	999999 ( 999999 )	4.75 ( 46.9 )	5.62 ( 27.7 )	6.94 ( 42.0 )	11.4 ( 56.1 )	13.1 ( 41.8 )	17.1 ( 63.6 )	5.48 ( 32.7 )	7.67 ( 8.44 )	999999 ( 999999 )	999999 ( 999999 )	999999 ( 999999 )	7.68 ( 45.4 )	( )	999999 ( 999999 )	6.51 ( 70.0 )	10.4 ( 59.4 )	11.2 ( 60.1 )

Notes
[52] - No subjects were analyzed in this arm for this endpoint.

No statistical analyses for this end point

Secondary: Phase Ia and Phase Ib: Objective response (OR)

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End point title

Phase Ia and Phase Ib: Objective response (OR)

End point description

OR was defined as best overall response (BOR) of complete response (CR) or partial response (PR) with tumour assessment during treatment period for each schedule. For DLBCL patients, a minor response according to Response Evaluation Criteria In Lymphoma 2017 (RECIL 2017) was not part of an objective response. BOR was determined from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent, according to the following criteria depending on the type of cancer: - solid tumour patients and mCRPC patients with measurable disease: CT and/ or MRI according to RECIST v1.1, every 2 cycles; - mCRPC patients without measurable disease: bone scan and PSA level according to Prostate Cancer Clinical Trials Working Group 3, every 4 cycles; - DLBCL patients:FDG-PET/CT scans according to RECIL 2017; every 2 cycles.

End point type

Secondary

End point timeframe

Up to 15 months for Phase 1a and up to 28 months for Phase Ib.

End point values	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Number of subjects analysed	2	2	3	6	6	2	6	6	13	4	15	12	8	4	2	2	2	12	14	11	20	22
Units: Participants	0	1	0	1	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	1	2

No statistical analyses for this end point

Secondary: Phase Ib: Progression-free survival or (PFS) or radiological PFS for mCRPC patients with non-measurable disease by RECIST v1.1

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End point title

Phase Ib: Progression-free survival or (PFS) or radiological PFS for mCRPC patients with non-measurable disease by RECIST v1.1 ^[53]

End point description

Progression-free survival (PFS) was defined as the time from date of start of BI 894999 to the date of objective disease progression ((PD) defined as 20% increase in the sum of the longest diameter of target lesions) or death, whichever is earlier for SCLC patients, CRC patients, mCRPC patients with measurable disease by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and NC patients, with tumour assessment every 2 cycles according to RECIST v1.1 during treatment period or Radiological PFS with tumour assessment by bone scan every 4 cycles for mCRPC patients with non-measurable disease by RECIST v1.1. For patients with ‘event’ as an outcome for PFS: - PFS [days] = date of outcome – date of first treatment administration + 1. For patients with ‘censored’ as an outcome for PFS: - PFS (censored) [days] = date of outcome – date of first treatment administration + 1. The Kaplan-Meier method was used to calculate the estimates.

End point type

Secondary

End point timeframe

Up to 28 months.

Notes
[53] - 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: Endpoint was specified only for metastatic Castration Resistant Prostate Cancer (mCRPC) patients in Phase Ib.

End point values	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Number of subjects analysed	12 ^[54]	14 ^[55]	11 ^[56]	20 ^[57]	22 ^[58]
Units: Weeks
median (confidence interval 95%)	5.6 (5.3 to 6.1)	5.6 (4.4 to 10.7)	11.9 (8.1 to 24.4)	6.9 (6.0 to 11.1)	7.8 (4.0 to 13.0)

Notes
[54] - Treated Set (TS) in Phase Ib dose expansion (TS PhIb).
[55] - TS PhIb
[56] - TS PhIb
[57] - TS PhIb
[58] - TS PhIb

No statistical analyses for this end point

Secondary: Phase Ib: Best overall response

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End point title

Phase Ib: Best overall response ^[59]

End point description

Best overall response (BOR) was determined from first treatment administration until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent, according to the following criteria depending on the type of cancer: - solid tumour patients and mCRPC patients with measurable disease: Computerized tomography (CT) and/ or magnetic resonance imaging (MRI) according to RECIST v1.1, every 2 cycles; - mCRPC patients without measurable disease: bone scan and PSA level according to Prostate Cancer Clinical Trials Working Group 3, every 4 cycles. Treated Set (TS) in Phase Ib dose expansion (TS PhIb): Included all patients in the TS who were treated in Phase Ib.

End point type

Secondary

End point timeframe

Imaging and assessment performed every 2 cycles (solid tumours patients) or 4 cycles (mCRPC patients) for the entire treatment period, up to 28 months.

Notes
[59] - 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: Endpoint was specified only for the participants of the Phase 1b.

End point values	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (SCLC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Number of subjects analysed	12	14	11	20	22
Units: Participants
Complete response	0	0	0	0	1
Partial response	0	0	1	1	1
Stable disease	1	2	2	7	6
Progressive disease	8	10	4	9	9
Not evaluable	3	2	4	3	5
Not assessed	0	0	0	0	0

No statistical analyses for this end point

Secondary: Phase Ib: Overall survival

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End point title

Phase Ib: Overall survival ^[60]

End point description

Overall survival (OS) was defined as the time from first administration of BI 894999 until death from any cause in patients with NUT carcinoma. For patients with ‘event’ as an outcome for OS: - OS [days] = date of outcome – date of first treatment administration + 1. For patients with ‘censored’ as an outcome for OS: - OS (censored) [days] = date of outcome – date of first treatment administration + 1. The Kaplan-Meier method was used to calculate the estimates. +(-)999999=NA-Could not be calculated due to low number of participants with missing values. Patients in NC Schedules B and C in Phase Ib dose expansion and after approval of protocol version 11.0 and gave consent to the collection of overall survival status.

End point type

Secondary

End point timeframe

Up to 28 months.

Notes
[60] - 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: Endpoint was specified only for NUT carcinoma patients in Phase Ib.

End point values	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule C: 6/3 or 7/3.5 mg BI 894999 (NC patients)
Number of subjects analysed	1	22
Units: Weeks
median (confidence interval 95%)	6.6 (-999999 to 999999)	15.4 (7.6 to 32.3)

No statistical analyses for this end point

Secondary: Phase Ib: Prostate Specific Antigen (PSA) response in patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

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End point title

Phase Ib: Prostate Specific Antigen (PSA) response in patients with Metastatic Castration Resistant Prostate Cancer (mCRPC) ^[61]

End point description

PSA response was defined as a decline in PSA value ≥50% from baseline (which is confirmed by a second value 3 to 4 weeks apart). mCRPC Schedule B in Phase Ib dose expansion (mCRPC): Included all mCRPC patients in the treated set who were treated in Phase Ib with Schedule B.

End point type

Secondary

End point timeframe

Up to 93 days.

Notes
[61] - 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: Endpoint was specified only for metastatic Castration Resistant Prostate Cancer (mCRPC) patients in Phase Ib.

End point values	Phase Ib - Schedule B: 2 or 2.5 mg BI 894999 (mCRPC patients)
Number of subjects analysed	11
Units: Participants	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

[Serious and Other Adverse Events]: From first date of dosing of study treatment until date of the last dosing of study treatment + 30 days residual effect period, up to 463 days for Phase 1a and up to 883 days for Phase Ib.

Adverse event reporting additional description

[All-Cause Mortality]: From first date of dosing until end of study, up to 1309 days for Phase Ia and up to 860 days for Phase Ib. Treated Set (TS): Included all patients who were dispensed study treatment and were documented to have taken at least one dose of the study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

24.1

Reporting group title

Phase Ia - Schedule A: 0.2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule A: 2 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule C: 6/3 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 6 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2 milligram (mg) of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally 2.5 mg of BI 894999 once daily, in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water. Schedule B was a continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule A: 0.5 mg BI 89499

Reporting group description

Reporting group title

Phase Ia - Schedule A: 5 mg BI 894999

Reporting group description

Reporting group title

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Reporting group description

Adult patients with a confirmed diagnosis of advanced, unresectable and/or metastatic malignant solid tumours who had failed conventional treatment or for whom no therapy of proven efficacy existed or who were not amenable to standard therapies were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (SCLC patients)

Reporting group description

Adult patients diagnosed with small cell lung cancer (SCLC) were administered 2.5 milligram (mg) of BI 894999 once daily. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Reporting group title

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Reporting group description

Adult patients with histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL) were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 5 milligram (mg) of BI 894999, followed by six days daily intake of the maintenance dose of 2.5 mg of BI 894999, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Reporting group title

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2 mg BI 894999 (SCLC patients)

Reporting group description

Adult patients diagnosed with small cell lung cancer (SCLC) were administered orally 2 milligram (mg) of BI 894999 once daily. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Reporting group title

Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Reporting group description

Reporting group title

Phase Ib - Schedule B: 2 mg BI 894999 (mCRPC patients)

Reporting group description

Adult patients diagnosed with metastatic castrate resistant prostate cancer (mCRPC) were administered orally 2 milligram (mg) of BI 894999 once daily. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days.

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (mCRPC patients)

Reporting group description

Adult patients diagnosed with metastatic castrate resistant prostate cancer (mCRPC) were administered orally 2.5 milligram (mg) of BI 894999 once daily. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Reporting group title

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Reporting group description

Adult patients diagnosed with colorectal cancer (CRC) were administered orally 2.5 milligram (mg) of BI 894999 once daily. BI 894999 administration was performed in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water according to Schedule B (continuous intake for 14 days followed by one week off treatment in cycles of 21 days).

Reporting group title

Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)

Reporting group description

This arm included adult patients diagnosed with NUT carcinoma (NC) who were administered orally once daily on Day 1 and on Day 15 of each cycle a loading dose of 7 milligram (mg) of BI 894999, followed by six days intake of the maintenance dose of 3.5 mg of BI 894999 once daily, followed by one week off, repeated every two weeks in cycles of 28 days (Schedule C). The loading and the maintenance dose were administered in the morning, after an overnight fast, 1 hour before breakfast with at least 250 milliliter (mL) of water.

Phase Ia - Schedule A: 0.2 mg BI 894999

Phase Ia - Schedule A: 1 mg BI 894999

Phase Ia - Schedule A: 1.5 mg BI 894999

Phase Ia - Schedule A: 2 mg BI 894999

Phase Ia - Schedule C: 6/3 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999

Phase Ia - Schedule B: 2 mg BI 894999

Phase Ia - Schedule B: 2.5 mg BI 894999

Phase Ia - Schedule C: 5/2.5 mg BI 894999

Phase Ia - Schedule A: 0.5 mg BI 89499

Phase Ia - Schedule A: 5 mg BI 894999

Phase Ia - Schedule C: 7/3.5 mg BI 894999

Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (SCLC patients)

Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)

Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients

Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)

Phase Ib - Schedule B: 2 mg BI 894999 (SCLC patients)

Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)

Phase Ib - Schedule B: 2 mg BI 894999 (mCRPC patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (mCRPC patients)

Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)

Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 2 (50.00%)

0 / 3 (0.00%)

3 / 6 (50.00%)

2 / 6 (33.33%)

8 / 15 (53.33%)

3 / 6 (50.00%)

6 / 13 (46.15%)

2 / 4 (50.00%)

2 / 2 (100.00%)

1 / 2 (50.00%)

8 / 12 (66.67%)

3 / 8 (37.50%)

2 / 3 (66.67%)

0 / 2 (0.00%)

1 / 2 (50.00%)

2 / 2 (100.00%)

2 / 4 (50.00%)

3 / 9 (33.33%)

12 / 21 (57.14%)

15 / 20 (75.00%)

1 / 1 (100.00%)

8 / 10 (80.00%)

8 / 14 (57.14%)

1 / 1 (100.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Cancer pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

3 / 20 (15.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant neoplasm progression

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 15 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Metastases to spinal cord

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour associated fever

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Embolism

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Jugular vein distension

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular occlusion

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Surgical and medical procedures

Euthanasia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Chest pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Death

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Disease progression

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Fatigue

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

1 / 1 (100.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Non-cardiac chest pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Bronchial obstruction

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

1 / 2 (50.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

2 / 21 (9.52%)

1 / 20 (5.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 3

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Epistaxis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Increased bronchial secretion

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngeal inflammation

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 3 (33.33%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Laryngeal obstruction

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

3 / 21 (14.29%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Pneumothorax

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary congestion

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary fistula

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

1 / 1 (100.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Delirium

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Investigations

Blood bilirubin increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatine phosphokinase MB increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood creatinine increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Electrocardiogram QT prolonged

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Electrocardiogram ST segment elevation

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Electrocardiogram T wave inversion

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

1 / 3 (33.33%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

2 / 20 (10.00%)

1 / 1 (100.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

1 / 1 (100.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

1 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Troponin I increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Troponin T increased

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

2 / 15 (13.33%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fracture

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tendon rupture

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac arrest

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Cardiac failure congestive

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiogenic shock

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Supraventricular tachycardia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebrovascular accident

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Headache

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

1 / 2 (50.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neuralgia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

2 / 20 (10.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Somnolence

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Syncope

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Anaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

2 / 12 (16.67%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 4 (25.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

2 / 3 (66.67%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

2 / 20 (10.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

3 / 3

0 / 0

1 / 1

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Eye haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Uveitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 4 (25.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Duodenal ulcer

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Lower gastrointestinal haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oral pain

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal haemorrhage

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

2 / 20 (10.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

3 / 14 (21.43%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary obstruction

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholangitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Dermatitis acneiform

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pruritus

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin necrosis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Acute kidney injury

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Bladder dilatation

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Calculus urinary

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haematuria

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary retention

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Osteonecrosis of jaw

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in jaw

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abdominal infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Bronchitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

COVID-19

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Cystitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

1 / 4 (25.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dacryocystitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (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 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Localised infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Meningitis pneumococcal

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Periorbital cellulitis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 21 (4.76%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 8 (12.50%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

1 / 21 (4.76%)

5 / 20 (25.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Spinal cord infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

1 / 13 (7.69%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 2 (50.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypercalcaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

3 / 20 (15.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

1 / 14 (7.14%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

0 / 10 (0.00%)

0 / 14 (0.00%)

0 / 1 (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

Hyponatraemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 21 (0.00%)

0 / 20 (0.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypophosphataemia

subjects affected / exposed

0 / 2 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 13 (0.00%)

0 / 4 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 8 (0.00%)

0 / 3 (0.00%)

0 / 2 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 21 (0.00%)

1 / 20 (5.00%)

0 / 1 (0.00%)

1 / 10 (10.00%)

0 / 14 (0.00%)

0 / 1 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Phase Ia - Schedule A: 0.2 mg BI 894999	Phase Ia - Schedule A: 1 mg BI 894999	Phase Ia - Schedule A: 1.5 mg BI 894999	Phase Ia - Schedule A: 2 mg BI 894999	Phase Ia - Schedule C: 6/3 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999	Phase Ia - Schedule B: 2 mg BI 894999	Phase Ia - Schedule B: 2.5 mg BI 894999	Phase Ia - Schedule C: 5/2.5 mg BI 894999	Phase Ia - Schedule A: 0.5 mg BI 89499	Phase Ia - Schedule A: 5 mg BI 894999	Phase Ia - Schedule C: 7/3.5 mg BI 894999	Phase Ia - Schedule B: 1.5 mg BI 894999 (DLBCL patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (SCLC patients)	Phase Ia - Schedule C: BI 894999 5/2.5 mg (DLBCL patients)	Phase Ia - Schedule C: 4/2 mg BI 894999 (DLBCL patients	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ia - Schedule B: 2.5 mg BI 894999 (DLBCL patients)	Phase Ib - Schedule B: 2 mg BI 894999 (SCLC patients)	Phase Ib - Schedule C: BI 894999 6/3 mg (NC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (NC patients)	Phase Ib - Schedule B: 2 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (mCRPC patients)	Phase Ib - Schedule B: 2.5 mg BI 894999 (CRC patients)	Phase Ib - Schedule C: BI 894999 7/3.5 mg (NC patients)
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 2 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	15 / 15 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	12 / 13 (92.31%)	4 / 4 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	12 / 12 (100.00%)	8 / 8 (100.00%)	3 / 3 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	4 / 4 (100.00%)	9 / 9 (100.00%)	21 / 21 (100.00%)	20 / 20 (100.00%)	1 / 1 (100.00%)	10 / 10 (100.00%)	14 / 14 (100.00%)	1 / 1 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	3	0	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Hypertension
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 13 (15.38%)	2 / 4 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 21 (19.05%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	1	0	2	0	0	0	3	2	2	1	0	3	0	0	0	0	0	0	0	4	0	0	2	2	0
Haematoma
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 2 (100.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 1 (100.00%)	1 / 10 (10.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	3	1	0	0	0	1	1	2	0
Orthostatic hypotension
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Pallor
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Chest discomfort
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Asthenia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	2 / 21 (9.52%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	0	0	0	3	0	1	0	0	0	1	3	1	0	1	3	0
Chest pain
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	1	1	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	2	0	0	0	1	0
Fatigue
subjects affected / exposed	2 / 2 (100.00%)	3 / 3 (100.00%)	4 / 6 (66.67%)	4 / 6 (66.67%)	8 / 15 (53.33%)	1 / 6 (16.67%)	3 / 6 (50.00%)	6 / 13 (46.15%)	2 / 4 (50.00%)	1 / 2 (50.00%)	2 / 2 (100.00%)	10 / 12 (83.33%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	3 / 4 (75.00%)	3 / 9 (33.33%)	10 / 21 (47.62%)	8 / 20 (40.00%)	0 / 1 (0.00%)	6 / 10 (60.00%)	6 / 14 (42.86%)	0 / 1 (0.00%)
occurrences all number	2	3	4	5	10	1	4	10	4	1	4	11	0	3	0	1	1	5	3	14	11	0	9	8	0
Facial pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Chills
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Gait disturbance
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
General physical health deterioration
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Generalised oedema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Malaise
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Hypothermia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 13 (23.08%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	3 / 10 (30.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	4	0	2	0	1	0	1	0	0	0	0	1	3	0	0	5	1	0
Non-cardiac chest pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	1	2	0	0	0	0	0	0	0	1	1	0	0	0	0
Pyrexia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 13 (15.38%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	5 / 21 (23.81%)	4 / 20 (20.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	1	2	1	0	0	0	3	0	1	1	2	0	0	6	7	0	1	0	0
Peripheral swelling
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Iodine allergy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Heavy menstrual bleeding
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Oedema genital
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Perineal pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Scrotal oedema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Testicular pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vulvovaginal discomfort
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	0	0
Cough
subjects affected / exposed	2 / 2 (100.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 15 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 13 (23.08%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	2 / 3 (66.67%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	5 / 21 (23.81%)	2 / 20 (10.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	3	0	0	0	3	0	1	4	1	0	0	1	1	2	0	0	1	0	3	7	2	0	1	3	0
Dyspnoea
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	5 / 13 (38.46%)	1 / 4 (25.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	2 / 3 (66.67%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	4 / 9 (44.44%)	1 / 21 (4.76%)	3 / 20 (15.00%)	0 / 1 (0.00%)	4 / 10 (40.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	1	1	1	1	1	0	2	5	1	1	0	5	1	2	0	1	0	0	5	1	4	0	6	5	0
Dyspnoea exertional
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	0 / 9 (0.00%)	4 / 21 (19.05%)	2 / 20 (10.00%)	1 / 1 (100.00%)	2 / 10 (20.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	1	1	0	1	0	1	0	0	0	0	2	0	0	1	0	0	3	0	5	2	1	2	1	0
Laryngeal inflammation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0
Nasal discomfort
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Pharyngeal inflammation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Pleural effusion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 13 (15.38%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	1	0	0	1	0	1
Rhinorrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	1	0
Psychiatric disorders
Affective disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Agitation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	4 / 20 (20.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	2	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	1	0
Confusional state
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0
Depression
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Insomnia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	1	0	0	2	0	0	0	1	0	0	0	0	1	0	0	0	0
Hallucination
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Personality change
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0	0	1	1
Activated partial thromboplastin time shortened
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	4 / 21 (19.05%)	6 / 20 (30.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0	0	1	0	0	1	1	0	0	0	2	7	8	0	0	1	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 21 (4.76%)	5 / 20 (25.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	1	0	0	1	1	0	0	0	1	3	6	1	0	1	2
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0	0	0	0	2	2	0	0	2	0
Blood antidiuretic hormone decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 15 (6.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	2 / 14 (14.29%)	1 / 1 (100.00%)
occurrences all number	0	0	0	2	2	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	0	0	2	2
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 13 (7.69%)	1 / 4 (25.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	5 / 20 (25.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	2	0	0	0	4	1	1	1	1	0	0	0	0	0	0	0	1	0	5	0	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0
Blood magnesium decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
C-reactive protein increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cardiac murmur
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Cortisol increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Echocardiogram abnormal
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Electrocardiogram PR prolongation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Electrocardiogram ST segment elevation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram T wave inversion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	5 / 20 (25.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	8	0	0	0	1
Lymphocyte count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	3 / 12 (25.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1	3	0	0	0	0	3	0	0	1	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	8	0	0	0	1	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	8 / 21 (38.10%)	8 / 20 (40.00%)	1 / 1 (100.00%)	2 / 10 (20.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	1	0	0	1	0	0	0	2	0	0	2	2	0	0	3	13	14	1	2	1	0
Prothrombin level decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Troponin I increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0
Troponin T increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 15 (6.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 13 (15.38%)	2 / 4 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	5 / 20 (25.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	4	2	1	1	2	3	0	0	3	0	1	0	0	0	1	0	2	6	0	1	0	0
Troponin increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	3	0	1	0	0	0	0	0	0	0	1	1	0
Urine output decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 13 (7.69%)	2 / 4 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	3 / 21 (14.29%)	0 / 20 (0.00%)	0 / 1 (0.00%)	4 / 10 (40.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	1	1	1	2	1	0	2	1	0	0	0	0	0	1	3	0	0	5	1	0
White blood cell count decreased
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	4 / 20 (20.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	7	0	0	6	6	0	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Face injury
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Infusion related reaction
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Limb injury
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Muscle rupture
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Overdose
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Post procedural haematoma
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Subcutaneous haematoma
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Tongue injury
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tooth fracture
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Urinary tract stoma complication
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Angina pectoris
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Palpitations
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	1	0	2	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0
Tachycardia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	2 / 21 (9.52%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	2	0	0	0	0
Ventricular arrhythmia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Agnosia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Amnesia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Cauda equina syndrome
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Disturbance in attention
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	3 / 20 (15.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0
Dizziness postural
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Headache
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 13 (23.08%)	1 / 4 (25.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	3 / 20 (15.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	1	0	0	1	0	1	5	1	3	2	2	1	0	0	0	0	0	0	4	4	0	0	1	0
Dysgeusia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 15 (6.67%)	0 / 6 (0.00%)	2 / 6 (33.33%)	3 / 13 (23.08%)	2 / 4 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	3 / 12 (25.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	3 / 21 (14.29%)	4 / 20 (20.00%)	0 / 1 (0.00%)	4 / 10 (40.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	1	0	0	2	1	0	2	3	2	0	1	3	1	0	2	0	0	0	3	4	5	0	5	3	0
Motor dysfunction
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Presyncope
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	1	0	0	0	1	0	0	0	0
Radiculopathy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	3	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	5 / 15 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	4 / 13 (30.77%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	6 / 12 (50.00%)	1 / 8 (12.50%)	1 / 3 (33.33%)	1 / 2 (50.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	6 / 21 (28.57%)	11 / 20 (55.00%)	1 / 1 (100.00%)	9 / 10 (90.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	0	0	1	1	7	4	3	4	0	1	0	8	1	1	3	1	1	0	0	10	18	4	15	4	0
Coagulopathy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Eosinophilia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Lymph node haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Lymph node pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 13 (23.08%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	3 / 8 (37.50%)	0 / 3 (0.00%)	2 / 2 (100.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 4 (50.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	2	0	0	0	10	0	0	1	1	3	0	3	0	0	3	1	0	3	0	2	0	0
Lymphopenia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	2	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	5 / 6 (83.33%)	8 / 15 (53.33%)	0 / 6 (0.00%)	3 / 6 (50.00%)	6 / 13 (46.15%)	2 / 4 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	7 / 12 (58.33%)	4 / 8 (50.00%)	2 / 3 (66.67%)	1 / 2 (50.00%)	0 / 2 (0.00%)	2 / 2 (100.00%)	4 / 4 (100.00%)	2 / 9 (22.22%)	5 / 21 (23.81%)	5 / 20 (25.00%)	0 / 1 (0.00%)	5 / 10 (50.00%)	5 / 14 (35.71%)	0 / 1 (0.00%)
occurrences all number	0	2	3	8	10	0	3	10	4	0	1	20	4	2	2	0	8	9	2	5	20	0	11	9	0
Ear and labyrinth disorders
Ear congestion
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ear haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ear pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Vitreous haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vision blurred
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Periorbital oedema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	1 / 4 (25.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	1	1	0	1	0	0	0	1	0	0	1	0	0	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	4 / 21 (19.05%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	3 / 14 (21.43%)	1 / 1 (100.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	0	1	2	2	0	0	0	0	1	1	5	1	0	0	6	1
Abdominal distension
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Anal fissure
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Anal haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Angular cheilitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Anal inflammation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	2	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Constipation
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 13 (15.38%)	1 / 4 (25.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	4 / 12 (33.33%)	2 / 8 (25.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 21 (19.05%)	5 / 20 (25.00%)	0 / 1 (0.00%)	3 / 10 (30.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	1	1	0	2	1	1	1	4	2	0	0	0	0	0	0	4	5	0	3	3	0
Diarrhoea
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	8 / 15 (53.33%)	3 / 6 (50.00%)	2 / 6 (33.33%)	6 / 13 (46.15%)	3 / 4 (75.00%)	1 / 2 (50.00%)	2 / 2 (100.00%)	3 / 12 (25.00%)	2 / 8 (25.00%)	0 / 3 (0.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)	3 / 4 (75.00%)	3 / 9 (33.33%)	9 / 21 (42.86%)	4 / 20 (20.00%)	0 / 1 (0.00%)	6 / 10 (60.00%)	8 / 14 (57.14%)	0 / 1 (0.00%)
occurrences all number	0	0	3	0	9	3	2	9	5	1	3	6	3	0	5	3	2	3	4	17	7	0	8	16	0
Dry mouth
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 13 (23.08%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	4 / 12 (33.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	3	0	0	0	4	0	0	1	0	0	0	0	0	1	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	1	0	0	0	0	1	0	2	0	0	0	1
Flatulence
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 21 (14.29%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	3	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Gastritis erosive
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0
Haemorrhoids
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Lip dry
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Melaena
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	4 / 15 (26.67%)	4 / 6 (66.67%)	2 / 6 (33.33%)	2 / 13 (15.38%)	1 / 4 (25.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	6 / 12 (50.00%)	1 / 8 (12.50%)	1 / 3 (33.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	2 / 4 (50.00%)	1 / 9 (11.11%)	4 / 21 (19.05%)	4 / 20 (20.00%)	0 / 1 (0.00%)	5 / 10 (50.00%)	6 / 14 (42.86%)	0 / 1 (0.00%)
occurrences all number	0	1	1	3	4	5	2	2	3	2	0	7	1	1	0	1	1	3	1	5	4	0	5	11	0
Odynophagia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Oral mucosal erythema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Retching
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	2 / 2 (100.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	1 / 1 (100.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	5	0	0	1	1	0	1	0	2	0	0	1	0	0	0	0	0	2	0	1	2	0	0
Subileus
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Toothache
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 15 (20.00%)	3 / 6 (50.00%)	2 / 6 (33.33%)	1 / 13 (7.69%)	1 / 4 (25.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	4 / 12 (33.33%)	1 / 8 (12.50%)	1 / 3 (33.33%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	2 / 9 (22.22%)	3 / 21 (14.29%)	1 / 20 (5.00%)	0 / 1 (0.00%)	6 / 10 (60.00%)	3 / 14 (21.43%)	0 / 1 (0.00%)
occurrences all number	0	5	1	1	3	6	5	1	2	1	0	5	1	2	0	1	0	1	3	3	1	0	6	7	0
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Hepatic cytolysis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hepatic pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis psoriasiform
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 13 (15.38%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	1	3	1	0	0	3	0	0	0	0	0	0	0	0	2	0	0	0	0
Dry skin
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	2 / 2 (100.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	3	1	0	0	0	0	1	0	2	0	0	0	0	2	0	0	0	1	0
Intertrigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Macule
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Night sweats
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	3	0	1	0	0
Eczema
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Prurigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pruritus
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	1	0	0	0	0	1	0	0	3	1	0	0	1	0
Psoriasis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Petechiae
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Skin ulcer
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Rash
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 13 (23.08%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	3	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Rash maculo-papular
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	3 / 21 (14.29%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	3	2	0	0	0	0
Purpura
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	1 / 1 (100.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1	0	0	0
Urticaria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	1 / 1 (100.00%)	3 / 10 (30.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	4	2	0
Pollakiuria
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0
Urinary tract pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Urinary retention
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Renal failure
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	3	0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 21 (14.29%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	4 / 21 (19.05%)	2 / 20 (10.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	2	0	0	0	0	0	0	0	1	4	2	0	2	0	0
Back pain
subjects affected / exposed	0 / 2 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 13 (15.38%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	3 / 21 (14.29%)	3 / 20 (15.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	1	1	0	0	0	1	2	0	0	0	2	0	0	1	1	0	0	0	4	4	0	1	1	0
Bone pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Flank pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 13 (15.38%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0
Muscle spasms
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	2	0	1	0	1	0	1	0	0	0	0	2	0
Myalgia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	1 / 20 (5.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	2	0	0	0	1	1	0	1	0	0
Neck pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 13 (15.38%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	1	1	2	0	0	0	0	0	0	1	0	0	0	0	0
Pubic pain
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 13 (15.38%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0
Bronchitis viral
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Clostridial infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Clostridium difficile colitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Erysipelas
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Diverticulitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genital herpes simplex
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Genital infection fungal
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Herpes dermatitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Impetigo
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Herpes zoster
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	1	0	0	1	0	0
Influenza
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Oesophageal infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Pharyngitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	1 / 20 (5.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	2	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2	0	0	0	0
Rash pustular
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 21 (9.52%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory tract infection bacterial
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tooth infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Tracheitis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0
Urinary tract infection enterococcal
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	1	0
Mucosal infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Stoma site infection
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	1 / 1 (100.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Acidosis
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Decreased appetite
subjects affected / exposed	1 / 2 (50.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	2 / 6 (33.33%)	4 / 15 (26.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	4 / 13 (30.77%)	1 / 4 (25.00%)	1 / 2 (50.00%)	2 / 2 (100.00%)	6 / 12 (50.00%)	1 / 8 (12.50%)	1 / 3 (33.33%)	0 / 2 (0.00%)	2 / 2 (100.00%)	1 / 2 (50.00%)	2 / 4 (50.00%)	2 / 9 (22.22%)	3 / 21 (14.29%)	5 / 20 (25.00%)	1 / 1 (100.00%)	6 / 10 (60.00%)	7 / 14 (50.00%)	0 / 1 (0.00%)
occurrences all number	1	1	3	2	4	1	2	4	2	1	3	7	1	2	0	3	1	2	4	3	5	1	8	8	0
Cell death
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dehydration
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fluid retention
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Folate deficiency
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gout
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 21 (19.05%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	3	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Hyperglycaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	1 / 4 (25.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	4 / 20 (20.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	2	0	1	3	0	0	0	0	0	0	0	0	6	0	0	1	0
Hyperphosphataemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	4	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	4 / 20 (20.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	11	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	2 / 20 (10.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	5	0	0	1	0
Hypokalaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	4 / 21 (19.05%)	3 / 20 (15.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	2 / 14 (14.29%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	4	1	1	0	0	0	0	1	0	0	0	0	0	0	0	7	5	0	1	2	0
Hypomagnesaemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	4 / 20 (20.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	1	2	1	1	0	0	0	0	0	0	0	0	0	0	0	0	1	4	0	1	0	0
Hyponatraemia
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 13 (0.00%)	0 / 4 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	5 / 21 (23.81%)	8 / 20 (40.00%)	0 / 1 (0.00%)	1 / 10 (10.00%)	1 / 14 (7.14%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	2	0	0	0	0	1	7	15	0	1	1	0
Hypophosphataemia
subjects affected / exposed	1 / 2 (50.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 15 (6.67%)	2 / 6 (33.33%)	3 / 6 (50.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	2 / 2 (100.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 3 (33.33%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 21 (4.76%)	3 / 20 (15.00%)	0 / 1 (0.00%)	2 / 10 (20.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	2	0	1	0	1	2	5	1	0	0	3	1	0	2	0	0	0	0	0	1	4	0	2	0	0
Malnutrition
subjects affected / exposed	0 / 2 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 13 (7.69%)	0 / 4 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 3 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 21 (0.00%)	0 / 20 (0.00%)	0 / 1 (0.00%)	0 / 10 (0.00%)	0 / 14 (0.00%)	0 / 1 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

02 Sep 2015

1st global protocol amendment: The potential Cytochrome P450 (CYP) inducing effect was addressed in the amended Clinical Trial Protocol (CTP) and a non-exhaustive list of CYP 3A4, 2C8 and 1A2 substrates was added (Section 10.6 of the CTP). Furthermore, it was added to inclusion criterion 6 that an additional barrier method is necessary for women of childbearing potential using a contraceptive pill due to the potential CYP3A4 inducing effect of BI 894999.

08 Apr 2016

2nd global protocol amendment: A second dosing schedule (Schedule B: 3-week cycles [21 days] with 2 weeks on treatment and 1 week off treatment) was introduced. The evaluation of BI 894999 (Schedule A: continuous dosing in 3-week cycles) in patients with Non-Hodgkin Lymphoma (NHL) was initiated. The secondary pharmacokinetics (PK) endpoints were reduced, and some secondary PK parameters were re-defined as further endpoints.

23 Nov 2016

3rd global protocol amendment: Precautionary measures were introduced because of cardiac findings in patients participating in the trial. The measures were applicable to all ongoing patients who had benefited from the treatment in order to allow them to continue the treatment under close cardiac safety monitoring. Further enrolment into the trial was stopped.

12 May 2017

4th global protocol amendment: External cardiologists concluded that the cause of the troponin elevation was unclear. Patients could continue on treatment with appropriate monitoring. Cardiac monitoring was adapted. Patients in the NHL cohort were be treated with the Schedule selected by the Data Monitoring Committee (DMC) once Maximum Tolerated dose (MTD) had been determined for both Schedules A and B in patients with solid tumours. The Dose Limiting Toxicity (DLT) definition was revised.

18 Oct 2017

5th global protocol amendment: Changes were introduced to restrict the definition of NHL to allow analyses of results in a more homogenous population. The NHL cohort was restricted to DLBCL patients. The protocol was amended to reflect the selection of 4 types of solid tumours (SCLC, mCRPC, CRC and NC) to be tested in the Phase 1b part of the study.

25 Jun 2018

6th global protocol amendment: The protocol was revised to clarify the significance of drug-related troponin Common Terminology Criteria for Adverse Events (CTCAE) grade 3.

05 Sep 2018

7th global protocol amendment: NC allowed inclusion of minor patients (aged ≥15 years at the time of consent). The NC cohort was also extended to up to 20 patients. NC patients who were progressing under trial treatment could continue with treatment if they derived clinical benefit and no other treatment option was available.

05 Nov 2018

8th global protocol amendment: Included clarifications and changes for consistency that were introduced following review of protocol version 7.0 by the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) authority in Germany and of protocol version 8.0 by the U.S. Food and Drug Administration (US FDA).

05 Feb 2019

9th global protocol amendment: A third intermittent dose escalation was added (Schedule C) in Phase Ia.

24 Sep 2019

10th global protocol amendment: If Schedule C appeared to have a better tolerability in patients with solid tumours than Schedule B, this could be extended to NC patients. Overall survival was added as an endpoint for patients with NC. Time to treatment failure was also added as an endpoint. Eligibility criteria were revised for including patients with NC due to their likely fast progression and the lack of any other treatment options in this indication. NC patients who had a mixed radiological response to treatment could remain on treatment if they derived clinical benefit.

24 Jun 2020

11th global protocol amendment: Due to the COVID-19 pandemic, the protocol was adapted to minimise in-patient visits.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
04 Oct 2016	On 04 Oct 2016, the sponsor decided to put a temporary hold on further recruitment of patients in trial 1367.1. The measure was taken since review of patient data revealed some patients with increased troponin levels. A thorough review by cardiologists was initiated with regards to troponin levels, Electrocardiogram (ECG), and clinical summaries of all enrolled patients. Evidence supporting a causal association between the increased laboratory troponin values and the administration of the trial medication could not be established. There were no corresponding clinically significant findings based on the reviewed ECGs and the clinical summaries of enrolled patients. The external review concluded that the cause of troponin elevation may be multifactorial in the trial patient population. In conclusion, the findings were considered to not preclude further clinical development. Consequently, patient recruitment was re-started on 25-April-2017. Ongoing patients continued the treatment during the time that recruitment was put on hold.	25 Apr 2017

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

This trial was closed in accordance with protocol-defined criteria for stopping the trial following assessments of futility. Trial was completed as described in protocol.

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Clinical trials

Clinical Trial Results: An open label, Phase Ia/Ib dose finding study with BI 894999 orally administered once a day in patients with advanced malignancies with repeated administration in patients with clinical benefit

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed in the first cycle

Primary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed in the first cycle

Primary: Phase Ib: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

Primary: Phase Ib: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

Secondary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

Secondary: Phase Ia: Number of patients with Dose Limiting Toxicities (DLTs) observed during the on-treatment period

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma over the time interval from 0 to 24 hours after administration of the first dose (AUC0-24)

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma over the time interval from 0 to 24 hours after administration of the first dose (AUC0-24)

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma after the first dose (Cmax)

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma after the first dose (Cmax)

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma at steady state over a uniform dosing interval τ (AUCτ, ss)

Secondary: Phase Ia and Phase Ib: Area under the concentration-time curve of BI 894999 in plasma at steady state over a uniform dosing interval τ (AUCτ, ss)

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma at steady state over a uniform dosing interval τ (Cmax, ss)

Secondary: Phase Ia and Phase Ib: Maximum measured concentration of BI 894999 in plasma at steady state over a uniform dosing interval τ (Cmax, ss)

Secondary: Phase Ia and Phase Ib: Objective response (OR)

Secondary: Phase Ia and Phase Ib: Objective response (OR)

Secondary: Phase Ib: Progression-free survival or (PFS) or radiological PFS for mCRPC patients with non-measurable disease by RECIST v1.1

Secondary: Phase Ib: Progression-free survival or (PFS) or radiological PFS for mCRPC patients with non-measurable disease by RECIST v1.1

Secondary: Phase Ib: Best overall response

Secondary: Phase Ib: Best overall response

Secondary: Phase Ib: Overall survival

Secondary: Phase Ib: Overall survival

Secondary: Phase Ib: Prostate Specific Antigen (PSA) response in patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Secondary: Phase Ib: Prostate Specific Antigen (PSA) response in patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
An open label, Phase Ia/Ib dose finding study with BI 894999 orally administered once a day in patients with advanced malignancies with repeated administration in patients with clinical benefit