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Clinical Trial Results:
A Phase I/II, open label, multicenter study of the safety and efficacy of LAG525 single agent and in combination with PDR001 administered to patients with advanced malignancies

Summary
EudraCT number	2015-000449-21
Trial protocol	BE ES DE FR IT
Global end of trial date	31 Dec 2020

Results information
Results version number	v2(current)
This version publication date	01 Mar 2022
First version publication date	26 Dec 2021
Other versions	v1
Version creation reason	Correction of full data set Correction of number of participants analyzed in two secondary endpoints.

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

CLAG525X2101C

ISRCTN number

US NCT number

NCT02460224

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

CH-4002, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.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 Dec 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Dec 2020

Was the trial ended prematurely?

Main objective of the trial

In the Phase 1 part, the primary objective was to estimate the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD) for the single-agent LAG525 (including Japanese patients) and for the combination of LAG525 and PDR001. In the Phase 2 part, the primary objective was to estimate the overall response rate (ORR) per Response Evaluation Criteria for Solid Tumors v 1.1 (RECIST v 1.1) for single-agent LAG525* and for the combination of LAG525 and PDR001. *: As the phase 2 expansion cohorts testing single-agent LAG525 were not opened, the Phase 2 objectives for single-agent LAG525 are not applicable.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Jun 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 26

Country: Number of subjects enrolled

Belgium: 47

Country: Number of subjects enrolled

Canada: 30

Country: Number of subjects enrolled

France: 7

Country: Number of subjects enrolled

Germany: 3

Country: Number of subjects enrolled

Hong Kong: 16

Country: Number of subjects enrolled

Italy: 55

Country: Number of subjects enrolled

Japan: 17

Country: Number of subjects enrolled

Singapore: 47

Country: Number of subjects enrolled

Spain: 77

Country: Number of subjects enrolled

Taiwan: 30

Country: Number of subjects enrolled

United States: 135

Worldwide total number of subjects

490

EEA total number of subjects

189

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)

341

From 65 to 84 years

149

85 years and over

Subject disposition

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Recruitment details

Participants took part in 25 investigative sites in 12 countries.

Screening details

The screening period began once patients had signed the study informed consent. All screening/baseline evaluations were performed ≤ 21 days before Cycle 1 Day 1, except for baseline radiological evaluations which had to be done within 28 days.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase 1: LAG525 1 mg/kg Q2W

Arm description

Single-agent LAG525 1 mg/kg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 1 mg/kg once every two weeks

Phase 1: LAG525 3 mg/kg Q2W

Arm description

Single-agent LAG525 3 mg/kg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 3 mg/kg once every two weeks

Phase 1: LAG525 5 mg/kg Q2W

Arm description

Single-agent LAG525 5 mg/kg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 5 mg/kg once every two weeks

Phase 1: LAG525 10 mg/kg Q2W

Arm description

Single-agent LAG525 10 mg/kg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 10 mg/kg once every two weeks

Phase 1: LAG525 15 mg/kg Q2W

Arm description

Single-agent LAG525 15 mg/kg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 15 mg/kg once every two weeks

Phase 1: LAG525 240 mg Q2W

Arm description

Single-agent LAG525 240 mg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 240 mg once every two weeks

Phase 1: LAG525 400 mg Q2W

Arm description

Single-agent LAG525 400 mg Q2W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 400 mg once every two weeks

Phase 1: LAG525 3 mg/kg Q4W

Arm description

Single-agent LAG525 3 mg/kg Q4W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 3 mg/kg once every four weeks

Phase 1: LAG525 5 mg/kg Q4W

Arm description

Single-agent LAG525 5 mg/kg Q4W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 5 mg/kg once every four weeks

Phase 1: LAG525 10 mg/kg Q4W

Arm description

Single-agent LAG525 10 mg/kg Q4W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 10 mg/kg once every four weeks

Phase 1: LAG525 400 mg Q4W

Arm description

Single-agent LAG525 400 mg Q4W

Arm type

Experimental

Investigational medicinal product name

LAG525

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

LAG525 400 mg once every four weeks

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Arm description

Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 0.3 mg/kg once every two weeks with PDR001 1 mg/kg once every two weeks

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Arm description

Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 1 mg/kg once every two weeks with PDR001 1 mg/kg once every two weeks

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Arm description

Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 80 mg once every two weeks with PDR001 80 mg once every two weeks

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Arm description

Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 80 mg once every two weeks with PDR001 240 mg once every two weeks

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Arm description

Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 240 mg once every two weeks with PDR001 240 mg once every two weeks

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Arm description

Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 240 mg once every three weeks with PDR001 300 mg once every three weeks

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Arm description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 400 mg once every three weeks with PDR001 300 mg once every three weeks

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Arm description

Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 600 mg once every three weeks with PDR001 300 mg once every three weeks

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Arm description

Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 80 mg once every four weeks with PDR001 240 mg once every four weeks

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Arm description

Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 400 mg once every four weeks with PDR001 400 mg once every four weeks

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Arm description

Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 800 mg once every four weeks with PDR001 400 mg once every four weeks

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Arm description

Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 1000 mg once every four weeks with PDR001 400 mg once every four weeks

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Arm description

Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 80 mg once every two weeks with PDR001 400 mg once every four weeks

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Arm description

Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 240 mg once every two weeks with PDR001 400 mg once every four weeks

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Arm description

Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 300 mg once every two weeks with PDR001 400 mg once every four weeks

Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Arm description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 400 mg once every three weeks with PDR001 300 mg once every three weeks

Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W

Arm description

Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 600 mg once every four weeks with PDR001 400 mg once every four weeks

Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Arm description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1

Arm type

Experimental

Investigational medicinal product name

LAG525+PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Combination of LAG525 400 mg once every three weeks with PDR001 300 mg once every three weeks

Number of subjects in period 1	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Started	17	12	6	6	6	30	30	5	6	11	5	6	6	6	5	6	20	6	12	7	6	12	6	11	6	6	121	21	93
ROW patients in the dose escalation	13	12	6	6	6	25	24	5	6	11	5	6	6	6	5	6	20	6	12	7	6	12	6	11	6	6	0	0	0
Japanese patients in the dose escalation	4	0	0	0	0	5	6	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	17	12	6	6	6	30	30	5	6	11	5	6	6	6	5	6	20	6	12	7	6	12	6	11	6	6	121	21	93
Adverse event, serious fatal	-	-	-	-	-	2	1	-	-	1	-	-	-	1	-	-	2	1	-	2	-	-	-	-	1	1	5	-	1
Physician decision	-	1	-	-	1	-	-	1	-	-	-	1	-	1	-	-	2	1	1	2	1	1	-	-	1	-	14	1	6
Adverse event, non-fatal	-	-	-	-	-	-	1	-	-	-	-	-	1	-	-	-	1	-	1	-	1	1	1	-	-	-	11	1	6
Progressive disease	15	11	5	6	3	26	28	4	5	9	5	4	5	4	5	5	15	3	8	3	4	9	4	11	4	5	85	17	77
Lost to follow-up	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-
Subject/guardian decision	2	-	1	-	2	2	-	-	1	1	-	1	-	-	-	1	-	1	2	-	-	1	-	-	-	-	6	2	3

Baseline characteristics

Top of page

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W

Reporting group description

Single-agent LAG525 1 mg/kg Q2W

Reporting group title

Phase 1: LAG525 3 mg/kg Q2W

Reporting group description

Single-agent LAG525 3 mg/kg Q2W

Reporting group title

Phase 1: LAG525 5 mg/kg Q2W

Reporting group description

Single-agent LAG525 5 mg/kg Q2W

Reporting group title

Phase 1: LAG525 10 mg/kg Q2W

Reporting group description

Single-agent LAG525 10 mg/kg Q2W

Reporting group title

Phase 1: LAG525 15 mg/kg Q2W

Reporting group description

Single-agent LAG525 15 mg/kg Q2W

Reporting group title

Phase 1: LAG525 240 mg Q2W

Reporting group description

Single-agent LAG525 240 mg Q2W

Reporting group title

Phase 1: LAG525 400 mg Q2W

Reporting group description

Single-agent LAG525 400 mg Q2W

Reporting group title

Phase 1: LAG525 3 mg/kg Q4W

Reporting group description

Single-agent LAG525 3 mg/kg Q4W

Reporting group title

Phase 1: LAG525 5 mg/kg Q4W

Reporting group description

Single-agent LAG525 5 mg/kg Q4W

Reporting group title

Phase 1: LAG525 10 mg/kg Q4W

Reporting group description

Single-agent LAG525 10 mg/kg Q4W

Reporting group title

Phase 1: LAG525 400 mg Q4W

Reporting group description

Single-agent LAG525 400 mg Q4W

Reporting group title

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1

Reporting group values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Total
Number of subjects	17	12	6	6	6	30	30	5	6	11	5	6	6	6	5	6	20	6	12	7	6	12	6	11	6	6	121	21	93	490
Age categorical
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	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	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	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	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	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	0	0	0	0	0	0	0
Adults (18-64 years)	12	4	2	4	4	23	24	3	4	8	4	5	6	6	4	3	12	3	8	5	4	10	5	9	4	5	75	20	65	341
From 65-84 years	5	8	4	2	2	7	6	2	2	3	1	1	0	0	1	3	8	3	4	2	2	2	1	2	2	1	46	1	28	149
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	56.1 ( 12.55 )	64.5 ( 12.43 )	61.8 ( 13.32 )	53.3 ( 20.76 )	61.2 ( 9.58 )	57.2 ( 10.94 )	56.7 ( 10.82 )	60.8 ( 9.36 )	54.8 ( 17.26 )	59.5 ( 7.16 )	60.4 ( 7.16 )	54.3 ( 8.78 )	58.0 ( 5.90 )	44.8 ( 5.23 )	58.2 ( 10.03 )	48.7 ( 24.36 )	59.1 ( 12.83 )	61.2 ( 11.34 )	61.3 ( 8.25 )	51.1 ( 12.03 )	59.8 ( 8.11 )	51.8 ( 12.10 )	59.2 ( 5.42 )	56.6 ( 10.31 )	60.7 ( 6.89 )	52.3 ( 12.50 )	61.0 ( 10.79 )	49.4 ( 8.94 )	58.4 ( 11.18 )	-
Sex: Female, Male
Units: participants
Female	7	6	3	4	4	17	14	2	4	6	2	3	3	2	1	3	9	3	11	3	3	7	5	6	4	3	53	20	40	248
Male	10	6	3	2	2	13	16	3	2	5	3	3	3	4	4	3	11	3	1	4	3	5	1	5	2	3	68	1	53	242
Race/Ethnicity, Customized
Units: Subjects
Caucasian	8	9	5	3	6	20	20	2	4	10	3	2	6	6	4	5	20	6	10	7	4	8	5	9	5	6	69	15	70	347
Black	1	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	0	1	1	4
Asian	8	2	1	3	0	10	10	1	1	0	2	3	0	0	1	1	0	0	2	0	2	2	1	2	1	0	48	4	17	122
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	0	0	0	0	0	1	1
Unknown	0	0	0	0	0	0	0	0	1	1	0	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	2	1	4	12
Other	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	4

End points

Top of page

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W

Reporting group description

Single-agent LAG525 1 mg/kg Q2W

Reporting group title

Phase 1: LAG525 3 mg/kg Q2W

Reporting group description

Single-agent LAG525 3 mg/kg Q2W

Reporting group title

Phase 1: LAG525 5 mg/kg Q2W

Reporting group description

Single-agent LAG525 5 mg/kg Q2W

Reporting group title

Phase 1: LAG525 10 mg/kg Q2W

Reporting group description

Single-agent LAG525 10 mg/kg Q2W

Reporting group title

Phase 1: LAG525 15 mg/kg Q2W

Reporting group description

Single-agent LAG525 15 mg/kg Q2W

Reporting group title

Phase 1: LAG525 240 mg Q2W

Reporting group description

Single-agent LAG525 240 mg Q2W

Reporting group title

Phase 1: LAG525 400 mg Q2W

Reporting group description

Single-agent LAG525 400 mg Q2W

Reporting group title

Phase 1: LAG525 3 mg/kg Q4W

Reporting group description

Single-agent LAG525 3 mg/kg Q4W

Reporting group title

Phase 1: LAG525 5 mg/kg Q4W

Reporting group description

Single-agent LAG525 5 mg/kg Q4W

Reporting group title

Phase 1: LAG525 10 mg/kg Q4W

Reporting group description

Single-agent LAG525 10 mg/kg Q4W

Reporting group title

Phase 1: LAG525 400 mg Q4W

Reporting group description

Single-agent LAG525 400 mg Q4W

Reporting group title

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients pre-treated with anti-PD-1/PD-L1

Primary: Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)

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End point title

Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment with single-agent LAG525 or within the first two cycles of treatment with the combination of LAG525 and PDR001. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.

End point type

Primary

End point timeframe

15 days for single-agent LAG525 arms and 30 days for the combination LAG525 + PDR001 arms

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this primary endpoint.
[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: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	16	12	6	5	6	28	27	5	6	11	5	6	6	5	5	5	17	4	9	5	6	11	6	11	5	6
Units: participants	1	0	2	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	1	1	0	0

No statistical analyses for this end point

Primary: Phase 2: Overall Response Rate (ORR) per RECIST 1.1

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End point title

Phase 2: Overall Response Rate (ORR) per RECIST 1.1 ^[3] ^[4]

End point description

Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. ORR is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Primary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis were planned for this primary endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: percentage of participants
number (confidence interval 90%)
Non-small cell lung cancer (NSCLC) (n=20,0,22)	15.0 (4.2 to 34.4)	999 (999 to 999)	0 (0.0 to 12.7)
Melanoma (n=20,0,22)	15.0 (4.2 to 34.4)	999 (999 to 999)	9.1 (1.6 to 25.9)
Renal cell cancer (RCC) (n=19,0,19)	26.3 (11.0 to 47.6)	999 (999 to 999)	5.3 (0.3 to 22.6)
Mesothelioma (n=41,0,16)	17.1 (8.3 to 29.7)	999 (999 to 999)	6.3 (0.3 to 26.4)
Triple negative breast cancer (TNBC) (n=21,21,14)	14.3 (4.0 to 32.9)	4.8 (0.2 to 20.7)	0 (0.0 to 19.3)

No statistical analyses for this end point

Secondary: Phase 1: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Phase 1: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[5]

End point description

Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants in each category (Rest of the World (ROW) patients, Japanese patients) with AEs and SAEs are reported in this record. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 4.5 years.

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[6]	12 ^[7]	6 ^[8]	6 ^[9]	6 ^[10]	30 ^[11]	30 ^[12]	5 ^[13]	6 ^[14]	11 ^[15]	5 ^[16]	6 ^[17]	6 ^[18]	6 ^[19]	5 ^[20]	6 ^[21]	20 ^[22]	6 ^[23]	12 ^[24]	7 ^[25]	6 ^[26]	12 ^[27]	6 ^[28]	11 ^[29]	6 ^[30]	6 ^[31]
Units: participants
AEs, ROW patients	13	11	6	6	6	24	24	5	6	11	5	6	6	6	5	6	19	6	12	7	6	12	6	11	6	6
SAEs, ROW patients	4	2	5	2	3	10	11	2	4	5	2	3	2	3	3	1	9	3	6	4	5	5	2	5	4	4
AEs, Japanese patients	4	999	999	999	999	5	6	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999
SAEs, Japanese patients	0	999	999	999	999	2	0	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999

Notes
[6] - n=13 ROW, 4 JP
[7] - n=12 ROW, 0 JP
[8] - n=6 ROW, 0 JP
[9] - n=6 ROW, 0 JP
[10] - n=6 ROW, 0 JP
[11] - n=25 ROW, 5 JP
[12] - n=24 ROW, 6 JP
[13] - n=5 ROW, 0 JP
[14] - n=6 ROW, 0 JP
[15] - n=11 ROW, 0 JP
[16] - n=5 ROW, 0 JP
[17] - n=6 ROW, 0 JP
[18] - n=6 ROW, 0 JP
[19] - n=6 ROW, 0 JP
[20] - n=5 ROW, 0 JP
[21] - n=6 ROW, 0 JP
[22] - n=20 ROW, 0 JP
[23] - n=6 ROW, 0 JP
[24] - n=12 ROW, 0 JP
[25] - n=7 ROW, 0 JP
[26] - n=6 ROW, 0 JP
[27] - n=12 ROW, 0 JP
[28] - n=6 ROW, 0 JP
[29] - n=11 ROW, 0 JP
[30] - n=6 ROW, 0 JP
[31] - n=6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

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End point title

Phase 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) ^[32]

End point description

Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The number of participants with AEs and SAEs is reported for each tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first dose of study treatment until last dose of study treatment plus 30 days post treatment, assessed up to 2.7 years.

Notes
[32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: participants
AEs, NSCLC (n=20,0,22)	19	999	22
SAEs, NSCLC (n=20,0,22)	13	999	7
AEs, Melanoma (n=20,0,22)	19	999	22
SAEs, Melanoma (n=20,0,22)	8	999	8
AEs, RCC (n=19,0,19)	19	999	19
SAEs, RCC (n=19,0,19)	14	999	5
AEs, Mesothelioma (n=41,0,16)	41	999	16
SAEs, Mesothelioma (n=41,0,16)	15	999	4
AEs, TNBC (n=21,21,14)	21	21	14
SAEs, TNBC (n=21,21,14)	9	10	4

No statistical analyses for this end point

Secondary: Phase 1: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

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End point title

Phase 1: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001 ^[33]

End point description

Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001. Japanese patients were not treated with PDR001 and therefore the dose reductions and dose interruptions of this study drug are not applicable. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years.

Notes
[33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[34]	12 ^[35]	6 ^[36]	6 ^[37]	6 ^[38]	30 ^[39]	30 ^[40]	5 ^[41]	6 ^[42]	11 ^[43]	5 ^[44]	6 ^[45]	6 ^[46]	6 ^[47]	5 ^[48]	6 ^[49]	20 ^[50]	6 ^[51]	12 ^[52]	7 ^[53]	6 ^[54]	12 ^[55]	6 ^[56]	11 ^[57]	6 ^[58]	6 ^[59]
Units: participants
LAG525 dose reduction, ROW patients	0	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
LAG525 dose interruption, ROW patients	2	2	1	1	1	1	1	1	0	2	0	4	1	2	1	1	6	2	2	1	2	3	0	4	1	1
PDR001 dose reduction, ROW patients	999	999	999	999	999	999	999	999	999	999	999	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
PDR001 dose interruption, ROW patients	999	999	999	999	999	999	999	999	999	999	999	4	1	2	1	0	6	2	2	1	2	3	0	3	0	1
LAG525 dose reduction, Japanese patients	0	999	999	999	999	0	0	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999
LAG525 dose interruption, Japanese patients	0	999	999	999	999	2	2	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999	999

Notes
[34] - n=13 ROW, 4 JP
[35] - n=12 ROW, 0 JP
[36] - n=6 ROW, 0 JP
[37] - n=6 ROW, 0 JP
[38] - n=6 ROW, 0 JP
[39] - n=25 ROW, 5 JP
[40] - n=24 ROW, 6 JP
[41] - n=5 ROW, 0 JP
[42] - n=6 ROW, 0 JP
[43] - n=11 ROW, 0 JP
[44] - n=5 ROW, 0 JP
[45] - n=6 ROW, 0 JP
[46] - n=6 ROW, 0 JP
[47] - n=6 ROW, 0 JP
[48] - n=5 ROW, 0 JP
[49] - n=6 ROW, 0 JP
[50] - n=20 ROW, 0 JP
[51] - n=6 ROW, 0 JP
[52] - n=12 ROW, 0 JP
[53] - n=7 ROW, 0 JP
[54] - n=6 ROW, 0 JP
[55] - n=12 ROW, 0 JP
[56] - n=6 ROW, 0 JP
[57] - n=11 ROW, 0 JP
[58] - n=6 ROW, 0 JP
[59] - n=6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

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End point title

Phase 2: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001 ^[60]

End point description

Number of participants with at least one dose reduction of LAG525, at least one dose interruption of LAG525, at least one dose reduction of PDR001 and at least one dose interruption of PDR001. The number of participants with dose reductions and dose interruptions of both study drugs is reported for each tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years.

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: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: participants
LAG525 dose reduction, NSCLC (n=20,0,22)	0	999	0
LAG525 dose interruption, NSCLC (n=20,0,22)	3	999	3
PDR001 dose reduction, NSCLC (n=20,0,22)	0	999	0
PDR001 dose interruption, NSCLC (n=20,0,22)	3	999	3
LAG525 dose reduction, melanoma (n=20,0,22)	0	999	0
LAG525 dose interruption, melanoma (n=20,0,22)	4	999	4
PDR001 dose reduction, melanoma (n=20,0,22)	0	999	0
PDR001 dose interruption, melanoma (n=20,0,22)	4	999	4
LAG525 dose reduction, RCC (n=19,0,19)	0	999	0
LAG525 dose interruption, RCC (n=19,0,19)	5	999	1
PDR001 dose reduction, RCC (n=19,0,19)	0	999	0
PDR001 dose interruption, RCC (n=19,0,19)	5	999	1
LAG525 dose reduction, mesothelioma (n=41,0,16)	0	999	0
LAG525 dose interruption, mesothelioma (n=41,0,16)	8	999	5
PDR001 dose reduction, mesothelioma (n=41,0,16)	0	999	0
PDR001 dose interruption, mesothelioma (n=41,0,16)	8	999	5
LAG525 dose reduction, TNBC (n=21,21,14)	0	0	0
LAG525 dose interruption, TNBC (n=21,21,14)	3	0	0
PDR001 dose reduction, TNBC (n=21,21,14)	0	0	0
PDR001 dose interruption, TNBC (n=21,21,14)	3	0	0

No statistical analyses for this end point

Secondary: Phase 1: Relative dose intensity (RDI) of LAG525 and PDR001

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End point title

Phase 1: Relative dose intensity (RDI) of LAG525 and PDR001 ^[61]

End point description

Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day). Japanese patients were not treated with PDR001 and therefore the RDI of this study drug is not applicable. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years.

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: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[62]	12 ^[63]	6 ^[64]	6 ^[65]	6 ^[66]	30 ^[67]	30 ^[68]	5 ^[69]	6 ^[70]	11 ^[71]	5 ^[72]	6 ^[73]	6 ^[74]	6 ^[75]	5 ^[76]	6 ^[77]	20 ^[78]	6 ^[79]	12 ^[80]	7 ^[81]	6 ^[82]	12 ^[83]	6 ^[84]	11 ^[85]	6 ^[86]	6 ^[87]
Units: percentage
arithmetic mean (standard deviation)
LAG525, ROW patients	98.9 ( 3.93 )	100 ( 0 )	94.4 ( 13.61 )	100 ( 0 )	98.2 ( 4.47 )	99.0 ( 5.00 )	99.9 ( 0.60 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	97.4 ( 6.27 )	100 ( 0 )	99.7 ( 0.84 )	100 ( 0 )	99.6 ( 0.93 )	97.8 ( 5.27 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	97.7 ( 7.54 )	100 ( 0 )	100 ( 0 )
PDR001, ROW patients	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	97.3 ( 6.72 )	100 ( 0 )	97.6 ( 5.00 )	100 ( 0 )	100 ( 0 )	98.0 ( 4.95 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )	100 ( 0 )
LAG525, Japanese patients	100 ( 0 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	98.0 ( 4.47 )	100 ( 0 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )

Notes
[62] - n=13 ROW, 4 JP
[63] - n=12 ROW, 0 JP
[64] - n=6 ROW, 0 JP
[65] - n=6 ROW, 0 JP
[66] - n=6 ROW, 0 JP
[67] - n=25 ROW, 5 JP
[68] - n=24 ROW, 6 JP
[69] - n=5 ROW, 0 JP
[70] - n=6 ROW, 0 JP
[71] - n=11 ROW, 0 JP
[72] - n=5 ROW, 0 JP
[73] - n=6 ROW, 0 JP
[74] - n=6 ROW, 0 JP
[75] - n=6 ROW, 0 JP
[76] - n=5 ROW, 0 JP
[77] - n=6 ROW, 0 JP
[78] - n=20 ROW, 0 JP
[79] - n=6 ROW, 0 JP
[80] - n=12 ROW, 0 JP
[81] - n=7 ROW, 0 JP
[82] - n=6 ROW, 0 JP
[83] - n=12 ROW, 0 JP
[84] - n=6 ROW, 0 JP
[85] - n=11 ROW, 0 JP
[86] - n=6 ROW, 0 JP
[87] - n=6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Relative dose intensity (RDI) of LAG525 and PDR001

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End point title

Phase 2: Relative dose intensity (RDI) of LAG525 and PDR001 ^[88]

End point description

Relative dose intensity of each study drug is calculated with the following formula: 100 x actual dose intensity (mg/day)/planned dose intensity (mg/day). The RDI of both study drugs is reported for each tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years.

Notes
[88] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: percentage
arithmetic mean (standard deviation)
LAG525, NSCLC patients (n=20,0,22)	100 ( 0 )	999 ( 999 )	100 ( 0 )
PDR001, NSCLC patients (n=20,0,22)	100 ( 0 )	999 ( 999 )	99.8 ( 0.71 )
LAG525, melanoma patients (n=20,0,22)	99.4 ( 2.80 )	999 ( 999 )	99.7 ( 1.47 )
PDR001, melanoma patients (n=20,0,22)	99.4 ( 2.80 )	999 ( 999 )	99.7 ( 1.47 )
LAG525, RCC patients (n=19,0,19)	100 ( 0 )	999 ( 999 )	100 ( 0 )
PDR001, RCC patients (n=19,0,19)	100 ( 0 )	999 ( 999 )	100 ( 0 )
LAG525, mesothelioma patients (n=41,0,16)	99.3 ( 4.26 )	999 ( 999 )	99.4 ( 1.99 )
PDR001, mesothelioma patients (n=41,0,16)	99.3 ( 4.26 )	999 ( 999 )	99.4 ( 1.99 )
LAG525, TNBC patients (n=21,21,14)	96.5 ( 11.08 )	100 ( 0 )	100 ( 0 )
PDR001, TNBC patients (n=21,21,14)	98.4 ( 7.21 )	100 ( 0 )	100 ( 0 )

No statistical analyses for this end point

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of LAG525

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End point title

Phase 1: Maximum observed serum concentration (Cmax) of LAG525 ^[89]

End point description

Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

pre-infusion, 1, 24, 168, 240 and 336 hours post-infusion, and 504 hours (Q3W regimens only) and 672 hours (Q4W regimens only) post infusion on Cycle 1 Day 1 and Cycle 3 Day 1. The duration of one cycle was 14 days (Q2W), 21 days (Q3W) and 28 days (Q4W).

Notes
[89] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[90]	12 ^[91]	6 ^[92]	6 ^[93]	6 ^[94]	29 ^[95]	30 ^[96]	5 ^[97]	6 ^[98]	11 ^[99]	5 ^[100]	6 ^[101]	6 ^[102]	6 ^[103]	5 ^[104]	6 ^[105]	20 ^[106]	5 ^[107]	11 ^[108]	7 ^[109]	4 ^[110]	10 ^[111]	6 ^[112]	11 ^[113]	6 ^[114]	6 ^[115]
Units: ug/mL
arithmetic mean (standard deviation)
Cycle 1, ROW patients	21.8 ( 6.52 )	72.4 ( 14.1 )	117 ( 26.7 )	247 ( 63.2 )	393 ( 95.2 )	73.8 ( 19.2 )	116 ( 28.3 )	66.4 ( 14.1 )	118 ( 23.8 )	268 ( 38.5 )	125 ( 38.9 )	8.58 ( 2.53 )	26.5 ( 3.6 )	24.1 ( 6.58 )	25.1 ( 6.81 )	87.9 ( 24.7 )	73.1 ( 14.7 )	122 ( 36.4 )	215 ( 43.9 )	27.2 ( 5.51 )	121 ( 8.96 )	276 ( 66.5 )	303 ( 82.3 )	27.1 ( 7.56 )	86.2 ( 22.2 )	73.1 ( 42.2 )
Cycle 3, ROW patients	34.7 ( 13.2 )	124 ( 30.5 )	272 ( 999 )	306 ( 999 )	607 ( 108 )	114 ( 36.5 )	169 ( 60.7 )	77.9 ( 11 )	117 ( 26.2 )	222 ( 0 )	250 ( 187 )	9.57 ( 4.91 )	31.6 ( 9.9 )	35.2 ( 7.29 )	33.8 ( 7.75 )	156 ( 70.4 )	88.7 ( 25.3 )	114 ( 19.8 )	274 ( 57.1 )	32 ( 17 )	174 ( 11.3 )	354 ( 118 )	513 ( 72.8 )	33.3 ( 14.5 )	96 ( 42.8 )	147 ( 43 )
Cycle 1, Japanese patients	23.1 ( 2.58 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	95.5 ( 18.3 )	152 ( 33.9 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )
Cycle 3, Japanese patients	32.6 ( 1.2 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	198 ( 999 )	255 ( 59.1 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )

Notes
[90] - n=12 (C1, ROW), 4 (C3, ROW), 4 (C1, JP), 2 (C3, JP)
[91] - n=12 (C1, ROW), 7 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[92] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[93] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[94] - n=6 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[95] - n=24 (C1, ROW), 9 (C3, ROW), 4 (C1, JP), 1 (C3, JP)
[96] - n=23 (C1, ROW), 9 (C3, ROW), 6 (C1, JP), 3 (C3, JP)
[97] - n=5 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[98] - n=6 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[99] - n=6 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[100] - n=5 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[101] - n=6 (C1, ROW), 3 (C3, ROW). No JP patients.
[102] - n=5 (C1, ROW), 4 (C3, ROW). No JP patients.
[103] - n=6 (C1, ROW), 3 (C3, ROW). No JP patients.
[104] - n=4 (C1, ROW), 3 (C3, ROW). No JP patients.
[105] - n=6 (C1, ROW), 4 (C3, ROW). No JP patients.
[106] - n=16 (C1, ROW), 14 (C3, ROW). No JP patients.
[107] - n=3 (C1, ROW), 2 (C3, ROW). No JP patients.
[108] - n=9 (C1, ROW), 5 (C3, ROW). No JP patients.
[109] - n=7 (C1, ROW), 3 (C3, ROW). No JP patients.
[110] - n=3 (C1, ROW), 2 (C3, ROW). No JP patients.
[111] - n=9 (C1, ROW), 4 (C3, ROW). No JP patients.
[112] - n=5 (C1, ROW), 2 (C3, ROW). No JP patients.
[113] - n=9 (C1, ROW), 6 (C3, ROW). No JP patients.
[114] - n=5 (C1, ROW), 5 (C3, ROW). No JP patients.
[115] - n=6 (C1, ROW), 3 (C3, ROW). No JP patients.

No statistical analyses for this end point

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of LAG525

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End point title

Phase 2: Maximum observed serum concentration (Cmax) of LAG525 ^[116]

End point description

End point type

Secondary

End point timeframe

Notes
[116] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: ug/mL
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=20,0,22)	154 ( 43.5 )	999 ( 999 )	106 ( 26.8 )
Cycle 3, NSCLC patients (n=15,0,15)	169 ( 51.9 )	999 ( 999 )	137 ( 30.8 )
Cycle 1, melanoma patients (n=20,0,21)	115 ( 29.9 )	999 ( 999 )	102 ( 36.7 )
Cycle 3, melanoma patients (n=13,0,14)	171 ( 32 )	999 ( 999 )	163 ( 52.8 )
Cycle 1, RCC patients (n=18,0,16)	118 ( 34.7 )	999 ( 999 )	111 ( 28.3 )
Cycle 3, RCC patients (n=13,0,11)	158 ( 45.4 )	999 ( 999 )	153 ( 43.5 )
Cycle 1, mesothelioma patients (n=40,0,15)	116 ( 31 )	999 ( 999 )	119 ( 37.6 )
Cycle 3, mesothelioma patients (n=32,0,15)	141 ( 39.7 )	999 ( 999 )	138 ( 33.1 )
Cycle 1, TNBC patients (n=21,21,13)	144 ( 32.4 )	207 ( 53.1 )	132 ( 26.7 )
Cycle 3, TNBC patients (n=10,4,9)	179 ( 65.2 )	190 ( 55 )	157 ( 33.2 )

No statistical analyses for this end point

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of LAG525

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End point title

Phase 1: Time to reach maximum serum concentration (Tmax) of LAG525 ^[117]

End point description

Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[117] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[118]

12 ^[119]

6 ^[120]

6 ^[121]

6 ^[122]

29 ^[123]

30 ^[124]

5 ^[125]

6 ^[126]

11 ^[127]

5 ^[128]

6 ^[129]

6 ^[130]

6 ^[131]

5 ^[132]

6 ^[133]

20 ^[134]

5 ^[135]

11 ^[136]

7 ^[137]

4 ^[138]

10 ^[139]

6 ^[140]

11 ^[141]

6 ^[142]

6 ^[143]

Units: days

median (full range (min-max))

Cycle 1, ROW patients

1.73 (1.5 to 2.45)

1.6 (1.1 to 2.62)

1.63 (1.17 to 2.13)

1.63 (1.5 to 2.35)

1.99 (1.48 to 2.07)

1.59 (1.5 to 2.17)

1.57 (1.47 to 2.45)

1.58 (1.03 to 2.25)

2.1 (1.5 to 2.17)

2.02 (1.5 to 2.28)

1.5 (1.5 to 1.68)

1.5 (1.5 to 1.65)

1.5 (0.933 to 1.53)

1.5 (1.47 to 1.52)

1.53 (1.5 to 1.58)

1.55 (1.5 to 2.03)

1.52 (1.02 to 4.25)

1.5 (1.5 to 1.58)

1.57 (1 to 4.45)

1.52 (1.5 to 1.55)

1.5 (1.5 to 1.5)

1.58 (1.5 to 2.07)

1.58 (1.5 to 2.1)

1.5 (1.5 to 2.57)

1.7 (1.57 to 2.08)

1.5 (0 to 1.55)

Cycle 3, ROW patients

1.83 (1.5 to 2.12)

2.05 (1.55 to 2.08)

1.08 (1.08 to 1.08)

1.55 (1.55 to 1.55)

1.67 (1.67 to 2.08)

1.58 (1.33 to 2.05)

1.5 (1.5 to 2.55)

2.08 (1.52 to 2.12)

1.93 (1.57 to 2.3)

1.83 (1.65 to 2)

1.5 (1.5 to 1.5)

1.72 (1.57 to 1.83)

1.51 (1.5 to 1.57)

1.5 (1.5 to 1.58)

1.5 (1.5 to 1.52)

1.53 (1.5 to 2)

1.53 (1.48 to 3.77)

1.58 (1.58 to 1.58)

1.52 (1 to 1.55)

1.58 (1.5 to 1.75)

1.54 (1.5 to 1.58)

1.58 (1.5 to 2.05)

1.75 (1.5 to 2)

1.53 (1.5 to 2.55)

1.58 (0 to 2)

1.58 (1.57 to 1.58)

Cycle 1, Japanese patients

1.58 (1.55 to 1.68)

999 (999 to 999)

1.54 (1.5 to 1.63)

1.54 (1.52 to 1.55)

999 (999 to 999)

Cycle 3, Japanese patients

1.63 (1.58 to 1.68)

999 (999 to 999)

1.57 (1.57 to 1.57)

1.6 (1.55 to 1.67)

999 (999 to 999)

Notes
[118] - n=12 (C1, ROW), 4 (C3, ROW), 4 (C1, JP), 2 (C3, JP)
[119] - n=12 (C1, ROW), 7 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[120] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[121] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[122] - n=6 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[123] - n=24 (C1, ROW), 9 (C3, ROW), 4 (C1, JP), 1 (C3, JP)
[124] - n=23 (C1, ROW), 9 (C3, ROW), 6 (C1, JP), 3 (C3, JP)
[125] - n=5 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[126] - n=6 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[127] - n=6 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[128] - n=5 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[129] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients
[130] - n=5 (C1, ROW), 4 (C3, ROW) No JP patients
[131] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients
[132] - n=4 (C1, ROW), 3 (C3, ROW) No JP patients
[133] - n=6 (C1, ROW), 4 (C3, ROW) No JP patients
[134] - n=16 (C1, ROW), 14 (C3, ROW) No JP patients
[135] - n=3 (C1, ROW), 2 (C3, ROW) No JP patients
[136] - n=9 (C1, ROW), 5 (C3, ROW) No JP patients
[137] - n=7 (C1, ROW), 3 (C3, ROW) No JP patients
[138] - n=3 (C1, ROW), 2 (C3, ROW) No JP patients
[139] - n=9 (C1, ROW), 4 (C3, ROW) No JP patients
[140] - n=5 (C1, ROW), 2 (C3, ROW) No JP patients
[141] - n=9 (C1, ROW), 6 (C3, ROW) No JP patients
[142] - n=5 (C1, ROW), 5 (C3, ROW) No JP patients
[143] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients

No statistical analyses for this end point

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of LAG525

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End point title

Phase 2: Time to reach maximum serum concentration (Tmax) of LAG525 ^[144]

End point description

End point type

Secondary

End point timeframe

Notes
[144] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: days
median (full range (min-max))
Cycle 1, NSCLC patients (n=20,0,22)	1.53 (0.917 to 3)	999 (999 to 999)	1.55 (0.917 to 2.62)
Cycle 3, NSCLC patients (n=15,0,15)	1.55 (1.45 to 2)	999 (999 to 999)	1.58 (1.5 to 2.33)
Cycle 1, melanoma patients (n=20,0,21)	1.51 (1.43 to 3)	999 (999 to 999)	1.53 (1.07 to 2.9)
Cycle 3, melanoma patients (n=13,0,14)	1.53 (1.45 to 2)	999 (999 to 999)	1.53 (0.683 to 1.82)
Cycle 1, RCC patients (n=18,0,16)	1.51 (1 to 3)	999 (999 to 999)	1.53 (1 to 2.05)
Cycle 3, RCC patients (n=13,0,11)	1.58 (1.48 to 2.08)	999 (999 to 999)	1.53 (1.45 to 2.8)
Cycle 1, mesothelioma patients (n=40,0,15)	1.53 (0.583 to 3)	999 (999 to 999)	1.55 (1.47 to 2.08)
Cycle 3, mesothelioma patients (n=32,0,15)	1.5 (0.967 to 2.13)	999 (999 to 999)	1.52 (1.42 to 2.08)
Cycle 1, TNBC patients (n=21,21,13)	1.53 (0.567 to 3)	1.53 (1.43 to 3)	1.58 (0.95 to 2)
Cycle 3, TNBC patients (n=10,4,9)	1.63 (1.48 to 2)	1.78 (1.7 to 1.92)	1.6 (1 to 2)

No statistical analyses for this end point

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

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End point title

Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525 ^[145]

End point description

Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[145] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[146]	12 ^[147]	6 ^[148]	6 ^[149]	6 ^[150]	29 ^[151]	30 ^[152]	5 ^[153]	6 ^[154]	11 ^[155]	5 ^[156]	6 ^[157]	6 ^[158]	6 ^[159]	5 ^[160]	6 ^[161]	20 ^[162]	5 ^[163]	11 ^[164]	7 ^[165]	4 ^[166]	10 ^[167]	6 ^[168]	11 ^[169]	6 ^[170]	6 ^[171]
Units: day*ug/mL
arithmetic mean (standard deviation)
Cycle 1, ROW patients	136 ( 49.2 )	506 ( 111 )	758 ( 172 )	1830 ( 627 )	2810 ( 555 )	500 ( 147 )	708 ( 199 )	631 ( 184 )	1220 ( 491 )	2230 ( 731 )	1290 ( 537 )	35.8 ( 10.5 )	174 ( 31.3 )	138 ( 38.9 )	162 ( 56.5 )	588 ( 196 )	608 ( 165 )	952 ( 441 )	1640 ( 539 )	198 ( 101 )	1040 ( 183 )	2890 ( 982 )	3020 ( 928 )	150 ( 61.6 )	484 ( 173 )	551 ( 205 )
Cycle 3, ROW patients	264 ( 146 )	1000 ( 358 )	2470 ( 999 )	2330 ( 999 )	5270 ( 1250 )	862 ( 583 )	1390 ( 759 )	928 ( 469 )	1200 ( 754 )	1770 ( 2230 )	2740 ( 2680 )	59.9 ( 39.3 )	286 ( 134 )	264 ( 133 )	234 ( 108 )	1310 ( 701 )	869 ( 328 )	1410 ( 831 )	1990 ( 1180 )	336 ( 439 )	2250 ( 44.7 )	3840 ( 1600 )	7160 ( 3190 )	211 ( 150 )	938 ( 141 )	1230 ( 617 )
Cycle 1, Japanese patients	144 ( 35.6 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	679 ( 142 )	1130 ( 153 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )
Cycle 3, Japanese patients	89.6 ( 76.7 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	1720 ( 999 )	2520 ( 359 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )

Notes
[146] - n=13 (C1, ROW), 4 (C3, ROW), 4 (C1, JP), 3 (C3, JP)
[147] - n=12 (C1, ROW), 7 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[148] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[149] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[150] - n=6 (C1, ROW), 4 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[151] - n=25 (C1, ROW), 11 (C3, ROW), 4 (C1, JP), 1 (C3, JP)
[152] - n=24 (C1, ROW), 9 (C3, ROW), 6 (C1, JP), 3 (C3, JP)
[153] - n=5 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[154] - n=6 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[155] - n=10 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[156] - n=5 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[157] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients
[158] - n=6 (C1, ROW), 5 (C3, ROW) No JP patients
[159] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients
[160] - n=5 (C1, ROW), 3 (C3, ROW) No JP patients
[161] - n=6 (C1, ROW), 4 (C3, ROW) No JP patients
[162] - n=19 (C1, ROW), 14 (C3, ROW) No JP patients
[163] - n=4 (C1, ROW), 3 (C3, ROW) No JP patients
[164] - n=9 (C1, ROW), 6 (C3, ROW) No JP patients
[165] - n=7 (C1, ROW), 3 (C3, ROW) No JP patients
[166] - n=3 (C1, ROW), 2 (C3, ROW) No JP patients
[167] - n=10 (C1, ROW), 4 (C3, ROW) No JP patients
[168] - n=6 (C1, ROW), 2 (C3, ROW) No JP patients
[169] - n=11 (C1, ROW), 7 (C3, ROW) No JP patients
[170] - n=6 (C1, ROW), 4 (C3, ROW) No JP patients
[171] - n=5 (C1, ROW), 5 (C3, ROW) No JP patients

No statistical analyses for this end point

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

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End point title

Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525 ^[172]

End point description

End point type

Secondary

End point timeframe

Notes
[172] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: day*ug/mL
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=20,0,22)	1260 ( 509 )	999 ( 999 )	955 ( 272 )
Cycle 3, NSCLC patients (n=16,0,16)	1500 ( 688 )	999 ( 999 )	1260 ( 554 )
Cycle 1, melanoma patients (n=20,0,22)	1030 ( 404 )	999 ( 999 )	953 ( 340 )
Cycle 3, melanoma patients (n=13,0,16)	1860 ( 507 )	999 ( 999 )	1680 ( 754 )
Cycle 1, RCC patients (n=19,0,17)	979 ( 366 )	999 ( 999 )	886 ( 429 )
Cycle 3, RCC patients (n=14,0,13)	1420 ( 678 )	999 ( 999 )	1280 ( 809 )
Cycle 1, mesothelioma patients (n=41,0,16)	963 ( 329 )	999 ( 999 )	1070 ( 350 )
Cycle 3, mesothelioma patients (n=34,0,16)	1400 ( 732 )	999 ( 999 )	1380 ( 729 )
Cycle 1, TNBC patients (n=21,21,14)	1180 ( 379 )	2010 ( 807 )	1150 ( 234 )
Cycle 3, TNBC patients (n=11,7,9)	1710 ( 1090 )	2800 ( 1210 )	1530 ( 578 )

No statistical analyses for this end point

Secondary: Phase 1: Terminal elimination half-life (T1/2) of LAG525

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End point title

Phase 1: Terminal elimination half-life (T1/2) of LAG525 ^[173]

End point description

Pharmacokinetic (PK) parameters were calculated based on LAG525 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[173] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	17 ^[174]	12 ^[175]	6 ^[176]	6 ^[177]	6 ^[178]	29 ^[179]	30 ^[180]	5 ^[181]	6 ^[182]	11 ^[183]	5 ^[184]	6 ^[185]	6 ^[186]	6 ^[187]	5 ^[188]	6 ^[189]	20 ^[190]	5 ^[191]	11 ^[192]	7 ^[193]	4 ^[194]	10 ^[195]	6 ^[196]	11 ^[197]	6 ^[198]	6 ^[199]
Units: days
arithmetic mean (standard deviation)
Cycle 1, ROW patients	7.65 ( 1.94 )	11.1 ( 4.12 )	9.99 ( 2.37 )	12 ( 4.5 )	12.8 ( 8 )	10.3 ( 3.5 )	11.5 ( 6.59 )	13.5 ( 4.07 )	13.1 ( 5.38 )	13.9 ( 5.15 )	13.6 ( 7.61 )	3.47 ( 1.4 )	9.15 ( 3.86 )	6.5 ( 3.25 )	7.52 ( 2.5 )	9.5 ( 2.78 )	11.5 ( 3.7 )	11.3 ( 4.94 )	10.2 ( 3.68 )	7.49 ( 4.42 )	15.7 ( 4.23 )	17.9 ( 7.88 )	14.4 ( 3.28 )	5.26 ( 2.43 )	9.12 ( 2.07 )	9.36 ( 2.18 )
Cycle 3, ROW patients	11.2 ( 2.62 )	14.4 ( 5.82 )	5.94 ( 999 )	12.2 ( 999 )	16.5 ( 2.87 )	12.1 ( 5.06 )	18 ( 9.7 )	15 ( 2.36 )	20.6 ( 8.51 )	20.8 ( 999 )	23.4 ( 14.6 )	6.15 ( 2.98 )	9.55 ( 3.95 )	9.17 ( 4.36 )	13.1 ( 0.736 )	14.7 ( 999 )	14.3 ( 7.02 )	14.5 ( 1.24 )	13.8 ( 4.45 )	11.1 ( 10.9 )	18.3 ( 3.58 )	15.1 ( 5.44 )	26.3 ( 11.9 )	7.32 ( 4.94 )	10.8 ( 1.76 )	15.1 ( 4.54 )
Cycle 1, Japanese patients	13.7 ( 10.2 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	9.42 ( 2.27 )	13.8 ( 4.38 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )
Cycle 3, Japanese patients	5.49 ( 2.38 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	19.4 ( 999 )	28.1 ( 18 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )	999 ( 999 )

Notes
[174] - n=11 (C1, ROW), 3 (C3, ROW), 4 (C1, JP), 2 (C3, JP)
[175] - n=12 (C1, ROW), 6 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[176] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[177] - n=6 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[178] - n=6 (C1, ROW), 3 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[179] - n=21 (C1, ROW), 7 (C3, ROW), 4 (C1, JP), 1 (C3, JP)
[180] - n=19 (C1, ROW), 8 (C3, ROW), 6 (C1, JP), 3 (C3, JP)
[181] - n=5 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[182] - n=6 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[183] - n=9 (C1, ROW), 1 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[184] - n=5 (C1, ROW), 2 (C3, ROW), 0 (C1, JP), 0 (C3, JP)
[185] - n=4 (C1, ROW), 3 (C3, ROW) No JP patients
[186] - n=6 (C1, ROW), 5 (C3, ROW) No JP patients
[187] - n=6 (C1, ROW), 3 (C3, ROW) No JP patients
[188] - n=5 (C1, ROW), 2 (C3, ROW) No JP patients
[189] - n=6 (C1, ROW), 1 (C3, ROW) No JP patients
[190] - n=18 (C1, ROW), 14 (C3, ROW) No JP patients
[191] - n=4 (C1, ROW), 2 (C3, ROW) No JP patients
[192] - n=9 (C1, ROW), 5 (C3, ROW) No JP patients
[193] - n=7 (C1, ROW), 2 (C3, ROW) No JP patients
[194] - n=3 (C1, ROW), 2 (C3, ROW) No JP patients
[195] - n=9 (C1, ROW), 3 (C3, ROW) No JP patients
[196] - n=6 (C1, ROW), 2 (C3, ROW) No JP patients
[197] - n=11 (C1, ROW), 6 (C3, ROW) No JP patients
[198] - n=5 (C1, ROW), 4 (C3, ROW) No JP patients
[199] - n=5 (C1, ROW), 4 (C3, ROW) No JP patients

No statistical analyses for this end point

Secondary: Phase 2: Terminal elimination half-life (T1/2) of LAG525

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End point title

Phase 2: Terminal elimination half-life (T1/2) of LAG525 ^[200]

End point description

End point type

Secondary

End point timeframe

Notes
[200] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	84	13	64
Units: days
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=17,0,13)	11.6 ( 6.11 )	999 ( 999 )	13.3 ( 4.62 )
Cycle 3, NSCLC patients (n=9,0,9)	16.3 ( 9.17 )	999 ( 999 )	15.9 ( 7.88 )
Cycle 1, melanoma patients (n=12,0,15)	15.6 ( 5.18 )	999 ( 999 )	15.5 ( 5.92 )
Cycle 3, melanoma patients (n=9,0,6)	20.1 ( 5.24 )	999 ( 999 )	19.2 ( 9.26 )
Cycle 1, RCC patients (n=13,0,11)	14.2 ( 3.61 )	999 ( 999 )	14.1 ( 5.39 )
Cycle 3, RCC patients (n=8,0,3)	14.1 ( 3.71 )	999 ( 999 )	23.1 ( 6.33 )
Cycle 1, mesothelioma patients (n=29,0,11)	13 ( 5.13 )	999 ( 999 )	13.7 ( 5.27 )
Cycle 3, mesothelioma patients (n=16,0,8)	18.4 ( 7.16 )	999 ( 999 )	18.7 ( 5.47 )
Cycle 1, TNBC patients (n=8,13,7)	22.5 ( 18.9 )	14.6 ( 3.82 )	14.4 ( 5.01 )
Cycle 3, TNBC patients (n=6,0,4)	18.7 ( 9.14 )	999 ( 999 )	19 ( 4.78 )

No statistical analyses for this end point

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of PDR001

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End point title

Phase 1: Maximum observed serum concentration (Cmax) of PDR001 ^[201]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose. Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[201] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[202]	0 ^[203]	0 ^[204]	0 ^[205]	0 ^[206]	0 ^[207]	0 ^[208]	0 ^[209]	0 ^[210]	0 ^[211]	0 ^[212]	6 ^[213]	6 ^[214]	6 ^[215]	5 ^[216]	6 ^[217]	20 ^[218]	5 ^[219]	11 ^[220]	7 ^[221]	4 ^[222]	10 ^[223]	6 ^[224]	11 ^[225]	6 ^[226]	6 ^[227]
Units: ug/mL
arithmetic mean (standard deviation)
Cycle 1, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	19.6 ( 3.59 )	19.6 ( 2.77 )	17.7 ( 3.84 )	58.8 ( 23.2 )	67.9 ( 20.4 )	76.2 ( 20 )	61.5 ( 22.1 )	85.1 ( 28 )	65 ( 11.3 )	87.6 ( 24.5 )	113 ( 26.8 )	116 ( 28.1 )	100 ( 23.1 )	115 ( 33.2 )	97.9 ( 17 )
Cycle 3, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	30.4 ( 11.9 )	28.7 ( 8.4 )	29.7 ( 9.97 )	89.5 ( 28.9 )	168 ( 20.1 )	97.5 ( 34.4 )	80 ( 25.1 )	123 ( 35.6 )	90.8 ( 51.2 )	142 ( 999 )	134 ( 56.7 )	167 ( 9.9 )	141 ( 58.2 )	147 ( 29.8 )	126 ( 27.2 )

Notes
[202] - No PDR001 dosing
[203] - No PDR001 dosing
[204] - No PDR001 dosing
[205] - No PDR001 dosing
[206] - No PDR001 dosing
[207] - No PDR001 dosing
[208] - No PDR001 dosing
[209] - No PDR001 dosing
[210] - No PDR001 dosing
[211] - No PDR001 dosing
[212] - No PDR001 dosing
[213] - n=5 (C1), 3 (C3)
[214] - n=5 (C1), 4 (C3)
[215] - n=6 (C1), 2 (C3)
[216] - n=5 (C1), 3 (C3)
[217] - n=6 (C1), 3 (C3)
[218] - n=14 (C1), 8 (C3)
[219] - n=4 (C1), 3 (C3)
[220] - n=11 (C1), 7 (C3)
[221] - n=7 (C1), 2 (C3)
[222] - n=4 (C1), 1 (C3)
[223] - n=8 (C1), 3 (C3)
[224] - n=5 (C1), 2 (C3)
[225] - n=9 (C1), 5 (C3)
[226] - n=5 (C1), 5 (C3)
[227] - n=6 (C1), 3 (C3)

No statistical analyses for this end point

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of PDR001

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End point title

Phase 2: Maximum observed serum concentration (Cmax) of PDR001 ^[228]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed serum concentration following a dose. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[228] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: ug/mL
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=20,0,20)	102 ( 33 )	999 ( 999 )	68.9 ( 17.3 )
Cycle 3, NSCLC patients (n=16,0,13)	118 ( 36.5 )	999 ( 999 )	100 ( 24.2 )
Cycle 1, melanoma patients (n=19,0,20)	75.7 ( 25.2 )	999 ( 999 )	71.3 ( 26.2 )
Cycle 3, melanoma patients (n=13,0,14)	117 ( 29.8 )	999 ( 999 )	105 ( 43.3 )
Cycle 1, RCC patients (n=18,0,15)	81 ( 21.3 )	999 ( 999 )	67 ( 25.8 )
Cycle 3, RCC patients (n=13,0,13)	104 ( 23.8 )	999 ( 999 )	103 ( 36.1 )
Cycle 1, mesothelioma patients (n=35,0,16)	70.5 ( 21.4 )	999 ( 999 )	82.7 ( 39 )
Cycle 3, mesothelioma patients (n=33,0,16)	96.5 ( 31.5 )	999 ( 999 )	113 ( 36.8 )
Cycle 1, TNBC patients (n=20,19,13)	91.5 ( 25.1 )	117 ( 36.7 )	89.8 ( 14.8 )
Cycle 3, TNBC patients (n=11,5,9)	124 ( 36.5 )	134 ( 54 )	123 ( 18.5 )

No statistical analyses for this end point

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of PDR001

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End point title

Phase 1: Time to reach maximum serum concentration (Tmax) of PDR001 ^[229]

End point description

End point type

Secondary

End point timeframe

Notes
[229] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[230]

0 ^[231]

0 ^[232]

0 ^[233]

0 ^[234]

0 ^[235]

0 ^[236]

0 ^[237]

0 ^[238]

0 ^[239]

0 ^[240]

6 ^[241]

6 ^[242]

6 ^[243]

5 ^[244]

6 ^[245]

20 ^[246]

5 ^[247]

11 ^[248]

7 ^[249]

4 ^[250]

10 ^[251]

6 ^[252]

11 ^[253]

6 ^[254]

6 ^[255]

Units: days

median (full range (min-max))

Cycle 1, ROW patients

( to )

1.5 (1.47 to 1.62)

1.5 (1.1 to 1.55)

1.55 (1.42 to 1.63)

1.63 (1.52 to 1.78)

1.51 (0.95 to 1.67)

1.53 (0.467 to 2.42)

1.75 (1.5 to 2.08)

1.53 (1.45 to 2.5)

1.58 (1.5 to 2.02)

1.5 (1.47 to 1.72)

1.66 (1.5 to 2.07)

1.5 (0.583 to 1.58)

1.5 (1.5 to 1.58)

1.58 (0.683 to 2.12)

1.56 (1.47 to 1.68)

Cycle 3, ROW patients

( to )

1.5 (1.07 to 1.65)

1.58 (1.57 to 1.68)

1.55 (1.52 to 1.58)

1.72 (1.57 to 17.2)

1.75 (1.58 to 2.08)

1.5 (0.45 to 1.72)

1.5 (1.5 to 1.62)

1.58 (1 to 2.13)

1.63 (1.58 to 1.67)

1.8 (1.8 to 1.8)

1.53 (1.45 to 2.08)

1.87 (1.57 to 2.17)

1.55 (1.52 to 1.6)

1.55 (0.533 to 2.12)

1.58 (1.52 to 1.68)

Notes
[230] - No PDR001 dosing
[231] - No PDR001 dosing
[232] - No PDR001 dosing
[233] - No PDR001 dosing
[234] - No PDR001 dosing
[235] - No PDR001 dosing
[236] - No PDR001 dosing
[237] - No PDR001 dosing
[238] - No PDR001 dosing
[239] - No PDR001 dosing
[240] - No PDR001 dosing
[241] - n=5 (C1), 3 (C3)
[242] - n=5 (C1), 4 (C3)
[243] - n=6 (C1), 2 (C3)
[244] - n=5 (C1), 3 (C3)
[245] - n=6 (C1), 3 (C3)
[246] - n=14 (C1), 8 (C3)
[247] - n=4 (C1), 3 (C3)
[248] - n=11 (C1), 7 (C3)
[249] - n=7 (C1), 2 (C3)
[250] - n=4 (C1), 1 (C3)
[251] - n=8 (C1), 3 (C3)
[252] - n=5 (C1), 2 (C3)
[253] - n=9 (C1), 5 (C3)
[254] - n=5 (C1), 5 (C3)
[255] - n=6 (C1), 3 (C3)

No statistical analyses for this end point

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of PDR001

Top of page

End point title

Phase 2: Time to reach maximum serum concentration (Tmax) of PDR001 ^[256]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) serum concentration following a dose. Actual recorded sampling times were considered for the calculations. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[256] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: days
median (full range (min-max))
Cycle 1, NSCLC patients (n=20,0,20)	1.57 (1.52 to 3)	999 (999 to 999)	1.57 (1 to 2.12)
Cycle 3, NSCLC patients (n=16,0,13)	1.57 (1.32 to 2.08)	999 (999 to 999)	1.58 (1.47 to 2.08)
Cycle 1, melanoma patients (n=19,0,20)	1.55 (0.35 to 3.08)	999 (999 to 999)	1.53 (0.567 to 2.5)
Cycle 3, melanoma patients (n=13,0,14)	1.57 (1.08 to 2.08)	999 (999 to 999)	1.53 (0.583 to 1.63)
Cycle 1, RCC patients (n=18,0,15)	1.58 (1 to 3.08)	999 (999 to 999)	1.57 (0.55 to 2)
Cycle 3, RCC patients (n=13,0,13)	1.53 (1.5 to 2.08)	999 (999 to 999)	1.58 (1.47 to 2)
Cycle 1, mesothelioma patients (n=35,0,16)	1.55 (0.483 to 3)	999 (999 to 999)	1.54 (0.5 to 2)
Cycle 3, mesothelioma patients (n=33,0,16)	1.52 (0.1 to 2.05)	999 (999 to 999)	1.5 (0.283 to 2.08)
Cycle 1, TNBC patients (n=20,19,13)	1.58 (0.5 to 3)	1.57 (1.45 to 2.92)	1.53 (0.967 to 2.08)
Cycle 3, TNBC patients (n=11,5,9)	1.6 (1.48 to 2.5)	1.75 (1.6 to 2.43)	1.65 (1.5 to 2.42)

No statistical analyses for this end point

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

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End point title

Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001 ^[257]

End point description

End point type

Secondary

End point timeframe

Notes
[257] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[258]	0 ^[259]	0 ^[260]	0 ^[261]	0 ^[262]	0 ^[263]	0 ^[264]	0 ^[265]	0 ^[266]	0 ^[267]	0 ^[268]	6 ^[269]	6 ^[270]	6 ^[271]	5 ^[272]	6 ^[273]	20 ^[274]	5 ^[275]	11 ^[276]	7 ^[277]	4 ^[278]	10 ^[279]	6 ^[280]	11 ^[281]	6 ^[282]	6 ^[283]
Units: day*ug/mL
arithmetic mean (standard deviation)
Cycle 1, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	114 ( 17 )	141 ( 45.4 )	134 ( 25.7 )	437 ( 177 )	466 ( 159 )	601 ( 238 )	537 ( 163 )	637 ( 263 )	591 ( 207 )	789 ( 319 )	1290 ( 441 )	1190 ( 353 )	1080 ( 412 )	1110 ( 335 )	950 ( 264 )
Cycle 3, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	292 ( 131 )	268 ( 151 )	289 ( 196 )	816 ( 472 )	1340 ( 673 )	1180 ( 447 )	1020 ( 563 )	939 ( 572 )	1500 ( 1450 )	1860 ( 150 )	1950 ( 645 )	2840 ( 531 )	1440 ( 828 )	1510 ( 874 )	1310 ( 700 )

Notes
[258] - No PDR001 dosing
[259] - No PDR001 dosing
[260] - No PDR001 dosing
[261] - No PDR001 dosing
[262] - No PDR001 dosing
[263] - No PDR001 dosing
[264] - No PDR001 dosing
[265] - No PDR001 dosing
[266] - No PDR001 dosing
[267] - No PDR001 dosing
[268] - No PDR001 dosing
[269] - n=6 (C1), 3 (C3)
[270] - n=6 (C1), 5 (C3)
[271] - n=6 (C1), 3 (C3)
[272] - n=5 (C1), 3 (C3)
[273] - n=6 (C1), 4 (C3)
[274] - n=18 (C1), 12 (C3)
[275] - n=5 (C1), 3 (C3)
[276] - n=11 (C1), 7 (C3)
[277] - n=7 (C1), 3 (C3)
[278] - n=4 (C1), 2 (C3)
[279] - n=10 (C1), 4 (C3)
[280] - n=6 (C1), 2 (C3)
[281] - n=11 (C1), 8 (C3)
[282] - n=6 (C1), 5 (C3)
[283] - n=6 (C1), 5 (C3)

No statistical analyses for this end point

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

Top of page

End point title

Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001 ^[284]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUC calculation. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[284] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	92
Units: day*ug/mL
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=20,0,22)	853 ( 347 )	999 ( 999 )	629 ( 197 )
Cycle 3, NSCLC patients (n=16,0,17)	1020 ( 500 )	999 ( 999 )	881 ( 443 )
Cycle 1, melanoma patients (n=20,0,22)	663 ( 291 )	999 ( 999 )	633 ( 310 )
Cycle 3, melanoma patients (n=13,0,16)	1390 ( 406 )	999 ( 999 )	1070 ( 537 )
Cycle 1, RCC patients (n=18,0,17)	739 ( 227 )	999 ( 999 )	617 ( 347 )
Cycle 3, RCC patients (n=14,0,14)	879 ( 547 )	999 ( 999 )	1060 ( 464 )
Cycle 1, mesothelioma patients (n=40,0,16)	633 ( 263 )	999 ( 999 )	747 ( 388 )
Cycle 3, mesothelioma patients (n=34,0,16)	1110 ( 500 )	999 ( 999 )	1110 ( 606 )
Cycle 1, TNBC patients (n=21,21,14)	808 ( 331 )	1110 ( 621 )	766 ( 277 )
Cycle 3, TNBC patients (n=11,7,9)	1370 ( 570 )	2150 ( 1180 )	1360 ( 351 )

No statistical analyses for this end point

Secondary: Phase 1: Terminal elimination half-life (T1/2) of PDR001

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End point title

Phase 1: Terminal elimination half-life (T1/2) of PDR001 ^[285]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant. Japanese patients were not treated with PDR001 and therefore the PK parameters of this study drug are not applicable. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[285] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[286]	0 ^[287]	0 ^[288]	0 ^[289]	0 ^[290]	0 ^[291]	0 ^[292]	0 ^[293]	0 ^[294]	0 ^[295]	0 ^[296]	6 ^[297]	6 ^[298]	6 ^[299]	5 ^[300]	6 ^[301]	20 ^[302]	5 ^[303]	11 ^[304]	7 ^[305]	4 ^[306]	10 ^[307]	6 ^[308]	11 ^[309]	6 ^[310]	6 ^[311]
Units: day
arithmetic mean (standard deviation)
Cycle 1, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	9.71 ( 8.24 )	10.2 ( 4.81 )	12.5 ( 3.38 )	20.7 ( 8.72 )	30.8 ( 47 )	22.8 ( 13.8 )	14.8 ( 4.78 )	11.8 ( 5 )	14 ( 3.72 )	15.1 ( 10.2 )	20.4 ( 8.41 )	18.7 ( 7.18 )	20.4 ( 10 )	14.6 ( 5.48 )	17.3 ( 2.76 )
Cycle 3, ROW patients	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	21.4 ( 9.4 )	22.3 ( 7.13 )	12.4 ( 10.3 )	17.8 ( 5.03 )	44.4 ( 36.8 )	27.7 ( 19.4 )	27.4 ( 4.25 )	17.4 ( 5.64 )	20.8 ( 12.4 )	22.4 ( 999 )	21.9 ( 4.22 )	32.8 ( 12.5 )	16.7 ( 10.2 )	16.1 ( 5.64 )	24.9 ( 6.75 )

Notes
[286] - No PDR001 dosing
[287] - No PDR001 dosing
[288] - No PDR001 dosing
[289] - No PDR001 dosing
[290] - No PDR001 dosing
[291] - No PDR001 dosing
[292] - No PDR001 dosing
[293] - No PDR001 dosing
[294] - No PDR001 dosing
[295] - No PDR001 dosing
[296] - No PDR001 dosing
[297] - n=4 (C1), 3 (C3)
[298] - n=6 (C1), 5 (C3)
[299] - n=6 (C1), 3 (C3)
[300] - n=5 (C1), 2 (C3)
[301] - n=6 (C1), 3 (C3)
[302] - n=16 (C1), 12 (C3)
[303] - n=5 (C1), 3 (C3)
[304] - n=11 (C1), 6 (C3)
[305] - n=7 (C1), 3 (C3)
[306] - n=4 (C1), 1 (C3)
[307] - n=10 (C1), 3 (C3)
[308] - n=6 (C1), 2 (C3)
[309] - n=11 (C1), 7 (C3)
[310] - n=6 (C1), 4 (C3)
[311] - n=6 (C1), 5 (C3)

No statistical analyses for this end point

Secondary: Phase 2: Terminal elimination half-life (T1/2) of PDR001

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End point title

Phase 2: Terminal elimination half-life (T1/2) of PDR001 ^[312]

End point description

Pharmacokinetic (PK) parameters were calculated based on PDR001 serum concentrations by using non-compartmental methods. Elimination half-life (T1/2) values were calculated as 0.693/terminal elimination rate constant. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not applicable values (eg. coefficient of variation when n=1) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Notes
[312] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	89	15	61
Units: days
arithmetic mean (standard deviation)
Cycle 1, NSCLC patients (n=19,0,14)	17.2 ( 10 )	999 ( 999 )	15.8 ( 5.65 )
Cycle 3, NSCLC patients (n=7,0,7)	16.8 ( 7.88 )	999 ( 999 )	24.5 ( 8.47 )
Cycle 1, melanoma patients (n=14,0,14)	29.1 ( 31.6 )	999 ( 999 )	20 ( 5.66 )
Cycle 3, melanoma patients (n=12,0,10)	24.2 ( 6.17 )	999 ( 999 )	25.6 ( 15.7 )
Cycle 1, RCC patients (n=13,0,9)	17.8 ( 4.77 )	999 ( 999 )	18.4 ( 7.3 )
Cycle 3, RCC patients (n=10,0,3)	18.4 ( 5.02 )	999 ( 999 )	24.2 ( 5.05 )
Cycle 1, mesothelioma patients (n=28,0,8)	19.1 ( 7.98 )	999 ( 999 )	25.6 ( 7.49 )
Cycle 3, mesothelioma patients	25.2 ( 14.5 )	999 ( 999 )	17.3 ( 8.11 )
Cycle 1, TNBC patients (n=15,0,7)	18.8 ( 8.33 )	21.3 ( 7.43 )	19.9 ( 6.24 )
Cycle 3, TNBC patients (n=6,2,4)	23.9 ( 17.1 )	22.2 ( 0.591 )	23.8 ( 5.64 )

No statistical analyses for this end point

Secondary: Phase 1: Number of participants with anti-LAG525 antibodies

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End point title

Phase 1: Number of participants with anti-LAG525 antibodies ^[313]

End point description

End point type

Secondary

End point timeframe

Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).

Notes
[313] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	14	11	4	5	6	21	17	4	6	7	5	5	6	5	5	5	15	3	8	6	3	9	5	10	6	5
Units: participants
ADA-negative at baseline	14	10	4	5	5	19	15	3	6	6	5	5	5	5	4	4	12	3	8	6	3	9	5	10	5	5
ADA-positive at post-baseline	6	0	2	1	0	2	0	2	0	0	2	3	1	2	2	1	1	1	1	4	0	0	0	5	1	1

No statistical analyses for this end point

Secondary: Phase 2: Number of participants with anti-LAG525 antibodies

Top of page

End point title

Phase 2: Number of participants with anti-LAG525 antibodies ^[314]

End point description

Validated immunoassays were used for screening and confirmation of the presence of anti-LAG525 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).

Notes
[314] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	106	16	80
Units: participants
ADA-negative baseline, NSCLC (n=20,0,20)	19	999	19
ADA-positive post-baseline, NSCLC (n=20,0,20)	4	999	2
ADA-negative baseline, melanoma (n=16,0,19)	15	999	19
ADA-positive post-baseline, melanoma (n=16,0,19)	1	999	0
ADA-negative baseline, RCC (n=17,0,15)	17	999	13
ADA-positive post-baseline, RCC (n=17,0,15)	0	999	1
ADA-negative baseline, mesothelioma (n=38,0,15)	35	999	13
ADA-positive postbaseline, mesothelioma(n=38,0,15)	3	999	1
ADA-negative baseline, TNBC (n=15,16,11)	15	15	11
ADA-positive post-baseline, TNBC (n=15,16,11)	2	0	1

No statistical analyses for this end point

Secondary: Phase 1: Number of participants with anti-PDR001 antibodies

Top of page

End point title

Phase 1: Number of participants with anti-PDR001 antibodies ^[315]

End point description

End point type

Secondary

End point timeframe

Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 4.4 years).

Notes
[315] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

End point values	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W
Number of subjects analysed	0 ^[316]	0 ^[317]	0 ^[318]	0 ^[319]	0 ^[320]	0 ^[321]	0 ^[322]	0 ^[323]	0 ^[324]	0 ^[325]	0 ^[326]	5	6	5	5	5	16	2	7	7	4	5	2	6	4	3
Units: participants
ADA-negative at baseline												5	6	5	4	5	14	2	7	7	4	5	2	6	3	3
ADA-positive at post-baseline (i.e. ADA incidence)												2	2	2	0	2	2	0	2	1	0	0	0	1	1	0

Notes
[316] - No PDR001 dosing
[317] - No PDR001 dosing
[318] - No PDR001 dosing
[319] - No PDR001 dosing
[320] - No PDR001 dosing
[321] - No PDR001 dosing
[322] - No PDR001 dosing
[323] - No PDR001 dosing
[324] - No PDR001 dosing
[325] - No PDR001 dosing
[326] - No PDR001 dosing

No statistical analyses for this end point

Secondary: Phase 2: Number of participants with anti-PDR001 antibodies

Top of page

End point title

Phase 2: Number of participants with anti-PDR001 antibodies ^[327]

End point description

Validated immunoassays were used for screening and confirmation of the presence of anti-PDR001 antibodies (ADA, anti-drug antibodies) in serum. Number of participants with ADA in each category is reported in this record. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

Baseline (pre-infusion on Cycle 1 Day 1) and post-baseline (assessed throughout the treatment up to maximum 2.6 years).

Notes
[327] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	108	14	82
Units: participants
ADA-negative baseline, NSCLC (n=20,0,22)	18	999	21
ADA-positive post-baseline, NSCLC (n=20,0,22)	6	999	4
ADA-negative baseline, melanoma (n=17,0,19)	16	999	19
ADA-positive post-baseline, melanoma (n=17,0,19)	5	999	0
ADA-negative baseline, RCC (n=17,0,15)	17	999	12
ADA-positive post-baseline, RCC (n=17,0,15)	2	999	0
ADA-negative baseline, mesothelioma (n=37,0,16)	32	999	11
ADA-positive postbaseline, mesothelioma(n=37,0,16)	6	999	2
ADA-negative baseline, TNBC (n=17,14,10)	17	13	9
ADA-positive post-baseline, TNBC (n=17,14,10)	5	1	0

No statistical analyses for this end point

Secondary: Phase 1: Overall Response Rate (ORR) per RECIST 1.1

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End point title

Phase 1: Overall Response Rate (ORR) per RECIST 1.1 ^[328]

End point description

Tumor response was based on local investigator assessment and the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. ORR is reported for ROW and Japanese patients. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years

Notes
[328] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[329]

12 ^[330]

6 ^[331]

6 ^[332]

6 ^[333]

30 ^[334]

30 ^[335]

5 ^[336]

6 ^[337]

11 ^[338]

5 ^[339]

6 ^[340]

6 ^[341]

6 ^[342]

5 ^[343]

6 ^[344]

20 ^[345]

6 ^[346]

12 ^[347]

7 ^[348]

6 ^[349]

12 ^[350]

6 ^[351]

11 ^[352]

6 ^[353]

6 ^[354]

Units: percentage of participants

number (confidence interval 90%)

ROW

0 (0.0 to 20.6)

0 (0.0 to 22.1)

0 (0.0 to 39.3)

0 (0.0 to 11.3)

0 (0.0 to 11.7)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

0 (0.0 to 23.8)

0 (0.0 to 45.1)

33.3 (6.3 to 72.9)

0 (0.0 to 39.3)

16.7 (0.9 to 58.2)

0 (0.0 to 45.1)

16.7 (0.9 to 58.2)

20.0 (7.1 to 40.1)

33.3 (6.3 to 72.9)

0 (0.0 to 22.1)

0 (0.0 to 34.8)

0 (0.0 to 39.3)

16.7 (3.0 to 43.8)

0 (0.0 to 39.3)

0 (0.0 to 23.8)

16.7 (0.9 to 58.2)

0 (0.0 to 39.3)

Japanese

0 (0.0 to 52.7)

999 (999 to 999)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

999 (999 to 999)

Notes
[329] - 13 ROW, 4 JP
[330] - 12 ROW, 0 JP
[331] - 6 ROW, 0 JP
[332] - 6 ROW, 0 JP
[333] - 6 ROW, 0 JP
[334] - 25 ROW, 5 JP
[335] - 24 ROW, 6 JP
[336] - 5 ROW, 0 JP
[337] - 6 ROW, 0 JP
[338] - 5 ROW, 11 JP
[339] - 5 ROW, 0 JP
[340] - 6 ROW, 0 JP
[341] - 6 ROW, 0 JP
[342] - 6 ROW, 0 JP
[343] - 5 ROW, 0 JP
[344] - 6 ROW, 0 JP
[345] - 20 ROW, 0 JP
[346] - 6 ROW, 0 JP
[347] - 12 ROW, 0 JP
[348] - 7 ROW, 0 JP
[349] - 6 ROW, 0 JP
[350] - 12 ROW, 0 JP
[351] - 6 ROW, 0 JP
[352] - 11 ROW, 0 JP
[353] - 6 ROW, 0 JP
[354] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 1: Overall Response Rate (ORR) per irRC

Top of page

End point title

Phase 1: Overall Response Rate (ORR) per irRC ^[355]

End point description

TTumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR). For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters. ORR is reported for ROW and Japanese patients. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years

Notes
[355] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[356]

12 ^[357]

6 ^[358]

6 ^[359]

6 ^[360]

30 ^[361]

30 ^[362]

5 ^[363]

6 ^[364]

11 ^[365]

5 ^[366]

6 ^[367]

6 ^[368]

6 ^[369]

5 ^[370]

6 ^[371]

20 ^[372]

6 ^[373]

12 ^[374]

7 ^[375]

6 ^[376]

12 ^[377]

6 ^[378]

11 ^[379]

6 ^[380]

6 ^[381]

Units: percentage of participants

number (confidence interval 90%)

ROW

0 (0.0 to 20.6)

0 (0.0 to 22.1)

0 (0.0 to 39.3)

0 (0.0 to 11.3)

0 (0.0 to 11.7)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

0 (0.0 to 23.8)

0 (0.0 to 45.1)

33.3 (6.3 to 72.9)

0 (0.0 to 39.3)

16.7 (0.9 to 58.2)

0 (0.0 to 45.1)

16.7 (0.9 to 58.2)

20.0 (7.1 to 40.1)

33.3 (6.3 to 72.9)

0 (0.0 to 22.1)

0 (0.0 to 34.8)

0 (0.0 to 39.3)

33.3 (12.3 to 60.9)

0 (0.0 to 39.3)

0 (0.0 to 23.8)

16.7 (0.9 to 58.2)

0 (0.0 to 39.3)

Japanese

0 (0.0 to 52.7)

999 (999 to 999)

0 (0.0 to 45.1)

0 (0.0 to 39.3)

999 (999 to 999)

Notes
[356] - 13 ROW, 4 JP
[357] - 12 ROW, 0 JP
[358] - 6 ROW, 0 JP
[359] - 6 ROW, 0 JP
[360] - 6 ROW, 0 JP
[361] - 25 ROW, 5 JP
[362] - 26 ROW, 4 JP
[363] - 5 ROW, 0 JP
[364] - 6 ROW, 0 JP
[365] - 11 ROW, 0 JP
[366] - 5 ROW, 0 JP
[367] - 6 ROW, 0 JP
[368] - 6 ROW, 0 JP
[369] - 6 ROW, 0 JP
[370] - 5 ROW, 0 JP
[371] - 6 ROW, 0 JP
[372] - 20 ROW, 0 JP
[373] - 6 ROW, 0 JP
[374] - 12 ROW, 0 JP
[375] - 7 ROW, 0 JP
[376] - 6 ROW, 0 JP
[377] - 12 ROW, 0 JP
[378] - 6 ROW, 0 JP
[379] - 11 ROW, 0 JP
[380] - 6 ROW, 0 JP
[381] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Overall Response Rate (ORR) per irRC

Top of page

End point title

Phase 2: Overall Response Rate (ORR) per irRC ^[382]

End point description

Tumor response was based on local investigator assessment and the assessment criteria was immune-related Response Criteria (irRC). ORR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR) or immune related Partial Response (irPR). For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters. ORR is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years

Notes
[382] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: percentage of participants
number (confidence interval 90%)
NSCLC (n=20,0,22)	15.0 (4.2 to 34.4)	999 (999 to 999)	0 (0.0 to 12.7)
Melanoma (n=20,0,22)	15.0 (4.2 to 34.4)	999 (999 to 999)	9.1 (1.6 to 25.9)
RCC (n=19,0,19)	26.3 (11.0 to 47.6)	999 (999 to 999)	5.3 (0.3 to 22.6)
Mesothelioma (n=41,0,16)	19.5 (10.1 to 32.5)	999 (999 to 999)	6.3 (0.3 to 26.4)
TNBC (n=21,21,14)	14.3 (4.0 to 32.9)	4.8 (0.2 to 20.7)	0 (0.0 to 19.3)

No statistical analyses for this end point

Secondary: Phase 1: Disease Control Rate (DCR) per RECIST 1.1

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End point title

Phase 1: Disease Control Rate (DCR) per RECIST 1.1 ^[383]

End point description

Tumor response was based on local investigator assessment and the assessment criteria was RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. DCR is reported for ROW and Japanese patients. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years

Notes
[383] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[384]

12 ^[385]

6 ^[386]

6 ^[387]

6 ^[388]

30 ^[389]

30 ^[390]

5 ^[391]

6 ^[392]

11 ^[393]

5 ^[394]

6 ^[395]

6 ^[396]

6 ^[397]

5 ^[398]

6 ^[399]

20 ^[400]

6 ^[401]

12 ^[402]

7 ^[403]

6 ^[404]

12 ^[405]

6 ^[406]

11 ^[407]

6 ^[408]

6 ^[409]

Units: percentage of participants

number (confidence interval 90%)

ROW

23.1 (6.6 to 49.5)

41.7 (18.1 to 68.5)

16.7 (0.9 to 58.2)

0 (0.0 to 39.3)

66.7 (27.1 to 93.7)

24.0 (11.0 to 42.0)

20.8 (8.6 to 38.9)

20.0 (1.0 to 65.7)

33.3 (6.3 to 72.9)

18.2 (3.3 to 47.0)

20.0 (1.0 to 65.7)

50.0 (15.3 to 84.7)

33.3 (6.3 to 72.9)

60.0 (18.9 to 92.4)

33.3 (6.3 to 72.9)

55.0 (34.7 to 74.1)

50.0 (15.3 to 84.7)

8.3 (0.4 to 33.9)

28.6 (5.3 to 65.9)

66.7 (27.1 to 93.7)

41.7 (18.1 to 68.5)

16.7 (0.9 to 58.2)

36.4 (13.5 to 65.0)

50.0 (15.3 to 84.7)

Japanese

25.0 (1.3 to 75.1)

999 (999 to 999)

40.0 (7.6 to 81.1)

16.7 (0.9 to 58.2)

999 (999 to 999)

Notes
[384] - 13 ROW, 4 JP
[385] - 12 ROW, 0 JP
[386] - 6 ROW, 0 JP
[387] - 6 ROW, 0 JP
[388] - 6 ROW, 0 JP
[389] - 25 ROW, 5 JP
[390] - 26 ROW, 4 JP
[391] - 5 ROW, 0 JP
[392] - 6 ROW, 0 JP
[393] - 11 ROW, 0 JP
[394] - 5 ROW, 0 JP
[395] - 6 ROW, 0 JP
[396] - 6 ROW, 0 JP
[397] - 6 ROW, 0 JP
[398] - 5 ROW, 0 JP
[399] - 6 ROW, 0 JP
[400] - 20 ROW, 0 JP
[401] - 6 ROW, 0 JP
[402] - 12 ROW, 0 JP
[403] - 7 ROW, 0 JP
[404] - 6 ROW, 0 JP
[405] - 12 ROW, 0 JP
[406] - 6 ROW, 0 JP
[407] - 11 ROW, 0 JP
[408] - 6 ROW, 0 JP
[409] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 1: Disease Control Rate (DCR) per irRC

Top of page

End point title

Phase 1: Disease Control Rate (DCR) per irRC ^[410]

End point description

Tumor response was based on local investigator assessment per irRC. DCR per irRC is defined as the percentage of participants with a best overall response of immune related Complete Response (irCR), immune related Partial Response (irPR) or immune related Stable Disease (irSD). For irRC, irCR=Disappearance of all non-nodal target lesions and non-target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; irPR= At least a 30% decrease in the sum of diameters of all target lesions including new target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for irPR or irCR nor an increase in lesions which would qualify for progression. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the column is greater than 0. Therefore, missing values (values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 4.4 years

Notes
[410] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[411]

12 ^[412]

6 ^[413]

6 ^[414]

6 ^[415]

30 ^[416]

30 ^[417]

5 ^[418]

6 ^[419]

11 ^[420]

5 ^[421]

6 ^[422]

6 ^[423]

6 ^[424]

5 ^[425]

6 ^[426]

20 ^[427]

6 ^[428]

12 ^[429]

7 ^[430]

6 ^[431]

12 ^[432]

6 ^[433]

11 ^[434]

6 ^[435]

6 ^[436]

Units: percentage of participants

number (confidence interval 90%)

ROW

30.8 (11.3 to 57.3)

33.3 (12.3 to 60.9)

16.7 (0.9 to 58.2)

0 (0.0 to 39.3)

50.0 (15.3 to 84.7)

28.0 (13.9 to 46.2)

33.3 (17.8 to 52.1)

20.0 (1.0 to 65.7)

33.3 (6.3 to 72.9)

18.2 (3.3 to 47.0)

20.0 (1.0 to 65.7)

50.0 (15.3 to 84.7)

66.7 (27.1 to 93.7)

50.0 (15.3 to 84.7)

60.0 (18.9 to 92.4)

33.3 (6.3 to 72.9)

55.0 (34.7 to 74.1)

50.0 (15.3 to 84.7)

8.3 (0.4 to 33.9)

28.6 (5.3 to 65.9)

66.7 (27.1 to 93.7)

50.0 (24.5 to 75.5)

33.3 (6.3 to 72.9)

36.4 (13.5 to 65.0)

50.0 (15.3 to 84.7)

Japanese

25.0 (1.3 to 75.1)

999 (999 to 999)

40.0 (7.6 to 81.1)

16.7 (0.9 to 58.2)

999 (999 to 999)

Notes
[411] - 13 ROW, 4 JP
[412] - 12 ROW, 0 JP
[413] - 6 ROW, 0 JP
[414] - 6 ROW, 0 JP
[415] - 6 ROW, 0 JP
[416] - 25 ROW, 5 JP
[417] - 24 ROW, 6 JP
[418] - 5 ROW, 0 JP
[419] - 6 ROW, 0 JP
[420] - 11 ROW, 0 JP
[421] - 5 ROW, 0 JP
[422] - 6 ROW, 0 JP
[423] - 6 ROW, 0 JP
[424] - 6 ROW, 0 JP
[425] - 5 ROW, 0 JP
[426] - 6 ROW, 0 JP
[427] - 20 ROW, 0 JP
[428] - 6 ROW, 0 JP
[429] - 12 ROW, 0 JP
[430] - 7 ROW, 0 JP
[431] - 6 ROW, 0 JP
[432] - 12 ROW, 0 JP
[433] - 6 ROW, 0 JP
[434] - 11 ROW, 0 JP
[435] - 6 ROW, 0 JP
[436] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Disease Control Rate (DCR) per RECIST 1.1

Top of page

End point title

Phase 2: Disease Control Rate (DCR) per RECIST 1.1 ^[437]

End point description

Tumor response was based on local investigator assessment and the assessment criteria was RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. DCR is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years

Notes
[437] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: percentage of participants
number (confidence interval 90%)
NSCLC (n=20,0,22)	50.0 (30.2 to 69.8)	999 (999 to 999)	50.0 (31.1 to 68.9)
Melanoma (n=20,0,22)	45.0 (25.9 to 65.3)	999 (999 to 999)	40.9 (23.3 to 60.5)
RCC (n=19,0,19)	63.2 (41.8 to 81.2)	999 (999 to 999)	42.1 (23.0 to 63.2)
Mesothelioma (n=41,0,16)	65.9 (51.9 to 78.0)	999 (999 to 999)	56.3 (33.3 to 77.3)
TNBC (n=21,21,14)	33.3 (16.8 to 53.6)	23.8 (9.9 to 43.7)	21.4 (6.1 to 46.6)

No statistical analyses for this end point

Secondary: Phase 2: Disease Control Rate (DCR) per irRC

Top of page

End point title

Phase 2: Disease Control Rate (DCR) per irRC ^[438]

End point description

End point type

Secondary

End point timeframe

From start of treatment until end of treatment, assessed up to 2.6 years

Notes
[438] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: percentage of participants
number (confidence interval 90%)
NSCLC (n=20,0,22)	60.0 (39.4 to 78.3)	999 (999 to 999)	50.0 (31.1 to 68.9)
Melanoma (n=20,0,22)	55.0 (34.7 to 74.1)	999 (999 to 999)	40.9 (23.3 to 60.5)
RCC (n=19,0,19)	68.4 (47.0 to 85.3)	999 (999 to 999)	42.1 (23.0 to 63.2)
Mesothelioma (n=41,0,16)	65.9 (51.9 to 78.0)	999 (999 to 999)	56.3 (33.3 to 77.3)
TNBC (n=21,21,14)	33.3 (16.8 to 53.6)	28.6 (13.2 to 48.7)	21.4 (6.1 to 46.6)

No statistical analyses for this end point

Secondary: Phase 1: Duration of Response (DOR) per RECIST 1.1

Top of page

End point title

Phase 1: Duration of Response (DOR) per RECIST 1.1 ^[439]

End point description

DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 4.4 years

Notes
[439] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[440]

0 ^[441]

0 ^[442]

0 ^[443]

0 ^[444]

0 ^[445]

0 ^[446]

0 ^[447]

0 ^[448]

0 ^[449]

0 ^[450]

0 ^[451]

0 ^[452]

0 ^[453]

0 ^[454]

0 ^[455]

0 ^[456]

0 ^[457]

0 ^[458]

Units: months

median (confidence interval 90%)

( to )

999 (999 to 999)

( to )

999 (999 to 999)

( to )

12.2 (-999 to 999)

999 (7.9 to 999)

18.4 (2.8 to 999)

( to )

6.5 (5.6 to 999)

( to )

999 (999 to 999)

( to )

Notes
[440] - No patients with PR or CR
[441] - No patients with PR or CR
[442] - No patients with PR or CR
[443] - No patients with PR or CR
[444] - No patients with PR or CR
[445] - No patients with PR or CR
[446] - No patients with PR or CR
[447] - No patients with PR or CR
[448] - No patients with PR or CR
[449] - No patients with PR or CR
[450] - No patients with PR or CR
[451] - No patients with PR or CR
[452] - No patients with PR or CR
[453] - No patients with PR or CR
[454] - No patients with PR or CR
[455] - No patients with PR or CR
[456] - No patients with PR or CR
[457] - No patients with PR or CR
[458] - No patients with PR or CR

No statistical analyses for this end point

Secondary: Phase 1: Duration of Response (DOR) per irRC

Top of page

End point title

Phase 1: Duration of Response (DOR) per irRC ^[459]

End point description

DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was irRC. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 4.4 years

Notes
[459] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

0 ^[460]

0 ^[461]

0 ^[462]

0 ^[463]

0 ^[464]

0 ^[465]

0 ^[466]

0 ^[467]

0 ^[468]

0 ^[469]

0 ^[470]

0 ^[471]

0 ^[472]

0 ^[473]

0 ^[474]

0 ^[475]

0 ^[476]

0 ^[477]

0 ^[478]

Units: months

median (confidence interval 90%)

( to )

999 (999 to 999)

( to )

999 (999 to 999)

( to )

12.2 (-999 to 999)

999 (7.9 to 999)

999 (999 to 999)

( to )

9.2 (4.4 to 999)

( to )

999 (999 to 999)

( to )

Notes
[460] - No patients with PR or CR
[461] - No patients with PR or CR
[462] - No patients with PR or CR
[463] - No patients with PR or CR
[464] - No patients with PR or CR
[465] - No patients with PR or CR
[466] - No patients with PR or CR
[467] - No patients with PR or CR
[468] - No patients with PR or CR
[469] - No patients with PR or CR
[470] - No patients with PR or CR
[471] - No patients with PR or CR
[472] - No patients with PR or CR
[473] - No patients with PR or CR
[474] - No patients with PR or CR
[475] - No patients with PR or CR
[476] - No patients with PR or CR
[477] - No patients with PR or CR
[478] - No patients with PR or CR

No statistical analyses for this end point

Secondary: Phase 2: Duration of Response (DOR) per RECIST 1.1

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End point title

Phase 2: Duration of Response (DOR) per RECIST 1.1 ^[479]

End point description

DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1. DOR is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first documented response (CR or PR) to first documented progression or death due to study indication, assessed up to 2.6 years

Notes
[479] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	21	1	4
Units: months
median (confidence interval 90%)
NSCLC (n=3,0,0)	5.0 (3.7 to 999)	999 (999 to 999)	999 (999 to 999)
Melanoma (n=3,0,2)	11.0 (4.2 to 999)	999 (999 to 999)	999 (18.2 to 999)
RCC (n=5,0,1)	999 (7.6 to 999)	999 (999 to 999)	999 (999 to 999)
Mesothelioma (n=7,0,1)	999 (5.8 to 999)	999 (999 to 999)	999 (999 to 999)
TNBC (n=3,1,0)	999 (7.6 to 999)	999 (999 to 999)	999 (999 to 999)

No statistical analyses for this end point

Secondary: Phase 2: Duration of Response (DOR) per irRC

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End point title

Phase 2: Duration of Response (DOR) per irRC ^[480]

End point description

DOR only applies to subjects for whom best overall response is immune related complete response (irCR) or immune related partial response (irPR). DOR is defined as the time from the date of first documented response (irCR or irPR) to the date of first documented progression or death due to study indication. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was irRC. DOR is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From first documented response (irCR or irPR) to first documented progression or death due to study indication, assessed up to 2.6 years

Notes
[480] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	22	1	4
Units: months
median (confidence interval 90%)
NSCLC (n=3,0,0)	999 (999 to 999)	999 (999 to 999)	999 (999 to 999)
Melanoma (n=3,0,2)	17.5 (11.0 to 999)	999 (999 to 999)	999 (18.2 to 999)
RCC (n=5,0,1)	999 (7.6 to 999)	999 (999 to 999)	999 (999 to 999)
Mesothelioma (n=8,0,1)	999 (5.8 to 999)	999 (999 to 999)	999 (999 to 999)
TNBC (n=3,1,0)	999 (7.6 to 999)	999 (999 to 999)	999 (999 to 999)

No statistical analyses for this end point

Secondary: Phase 1: Progression-free survival (PFS) per RECIST 1.1

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End point title

Phase 1: Progression-free survival (PFS) per RECIST 1.1 ^[481]

End point description

PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1. PFS is reported for ROW and Japanese patients. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years

Notes
[481] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[482]

12 ^[483]

6 ^[484]

6 ^[485]

6 ^[486]

30 ^[487]

30 ^[488]

5 ^[489]

6 ^[490]

11 ^[491]

5 ^[492]

6 ^[493]

6 ^[494]

6 ^[495]

5 ^[496]

6 ^[497]

20 ^[498]

6 ^[499]

12 ^[500]

7 ^[501]

6 ^[502]

12 ^[503]

6 ^[504]

11 ^[505]

6 ^[506]

6 ^[507]

Units: months

median (confidence interval 90%)

ROW

1.8 (1.6 to 2.0)

2.3 (1.7 to 3.5)

1.6 (0.8 to 1.9)

1.9 (1.6 to 999)

7.9 (1.3 to 999)

1.7 (1.6 to 1.9)

1.8 (1.5 to 1.9)

2.8 (1.6 to 999)

2.1 (0.3 to 999)

1.8 (1.0 to 2.0)

1.5 (1.4 to 999)

3.8 (1.3 to 999)

1.9 (1.8 to 3.5)

1.8 (1.1 to 3.4)

8.4 (1.7 to 999)

1.8 (1.6 to 999)

2.8 (2.0 to 4.2)

6.5 (0.6 to 999)

1.4 (0.6 to 1.8)

1.8 (1.2 to 2.5)

3.1 (1.0 to 5.0)

2.3 (1.6 to 5.7)

1.5 (0.9 to 999)

1.9 (1.7 to 2.9)

3.8 (1.6 to 7.6)

3.2 (1.7 to 5.8)

Japanese

1.8 (1.2 to 999)

999 (999 to 999)

1.8 (1.0 to 999)

1.7 (1.2 to 1.8)

999 (999 to 999)

Notes
[482] - 13 ROW, 4 JP
[483] - 12 ROW, 0 JP
[484] - 6 ROW, 0 JP
[485] - 6 ROW, 0 JP
[486] - 6 ROW, 0 JP
[487] - 25 ROW, 5 JP
[488] - 26 ROW, 4 JP
[489] - 5 ROW, 0 JP
[490] - 6 ROW, 0 JP
[491] - 11 ROW, 0 JP
[492] - 5 ROW, 0 JP
[493] - 6 ROW, 0 JP
[494] - 6 ROW, 0 JP
[495] - 6 ROW, 0 JP
[496] - 5 ROW, 0 JP
[497] - 6 ROW, 0 JP
[498] - 20 ROW, 0 JP
[499] - 6 ROW, 0 JP
[500] - 12 ROW, 0 JP
[501] - 7 ROW, 0 JP
[502] - 6 ROW, 0 JP
[503] - 12 ROW, 0 JP
[504] - 6 ROW, 0 JP
[505] - 11 ROW, 0 JP
[506] - 6 ROW, 0 JP
[507] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 1: Progression-free survival (PFS) per irRC

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End point title

Phase 1: Progression-free survival (PFS) per irRC ^[508]

End point description

PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was irRC. PFS is reported for ROW and Japanese patients. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment to first documented progression or death due to any cause, assessed up to 4.4 years

Notes
[508] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 1 only.

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Number of subjects analysed

17 ^[509]

12 ^[510]

6 ^[511]

6 ^[512]

6 ^[513]

30 ^[514]

30 ^[515]

5 ^[516]

6 ^[517]

11 ^[518]

5 ^[519]

6 ^[520]

6 ^[521]

6 ^[522]

5 ^[523]

6 ^[524]

20 ^[525]

6 ^[526]

12 ^[527]

7 ^[528]

6 ^[529]

12 ^[530]

6 ^[531]

11 ^[532]

6 ^[533]

6 ^[534]

Units: months

median (confidence interval 90%)

ROW

1.9 (1.6 to 2.7)

1.9 (1.7 to 3.4)

1.6 (0.8 to 1.9)

1.9 (1.6 to 999)

3.4 (1.3 to 999)

1.8 (1.6 to 1.9)

1.9 (1.5 to 2.3)

2.8 (1.6 to 999)

2.6 (1.6 to 999)

1.8 (1.0 to 2.0)

1.5 (1.4 to 999)

3.8 (1.3 to 999)

4.2 (1.8 to 999)

2.6 (1.1 to 999)

8.4 (1.7 to 999)

1.8 (1.6 to 999)

2.8 (2.0 to 4.2)

7.5 (0.6 to 999)

1.6 (0.6 to 1.8)

2.0 (1.5 to 2.5)

3.1 (1.0 to 5.0)

3.2 (1.7 to 9.1)

1.5 (0.9 to 999)

2.0 (1.7 to 4.2)

3.8 (1.6 to 7.6)

3.2 (1.7 to 5.8)

Japanese

1.8 (1.2 to 999)

999 (999 to 999)

1.8 (1.0 to 999)

1.7 (1.2 to 1.8)

999 (999 to 999)

Notes
[509] - 13 ROW, 4 JP
[510] - 12 ROW, 0 JP
[511] - 6 ROW, 0 JP
[512] - 6 ROW, 0 JP
[513] - 6 ROW, 0 JP
[514] - 25 ROW, 5 JP
[515] - 26 ROW, 4 JP
[516] - 5 ROW, 0 JP
[517] - 6 ROW, 0 JP
[518] - 11 ROW, 0 JP
[519] - 5 ROW, 0 JP
[520] - 6 ROW, 0 JP
[521] - 6 ROW, 0 JP
[522] - 6 ROW, 0 JP
[523] - 5 ROW, 0 JP
[524] - 6 ROW, 0 JP
[525] - 20 ROW, 0 JP
[526] - 6 ROW, 0 JP
[527] - 12 ROW, 0 JP
[528] - 7 ROW, 0 JP
[529] - 6 ROW, 0 JP
[530] - 12 ROW, 0 JP
[531] - 6 ROW, 0 JP
[532] - 11 ROW, 0 JP
[533] - 6 ROW, 0 JP
[534] - 6 ROW, 0 JP

No statistical analyses for this end point

Secondary: Phase 2: Progression-free survival (PFS) per RECIST 1.1

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End point title

Phase 2: Progression-free survival (PFS) per RECIST 1.1 ^[535]

End point description

PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was RECIST 1.1. PFS is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years

Notes
[535] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: months
median (confidence interval 90%)
NSCLC (n=20,0,22)	3.9 (1.7 to 5.6)	999 (999 to 999)	3.5 (1.9 to 4.9)
Melanoma (n=20,0,22)	2.2 (1.6 to 5.6)	999 (999 to 999)	1.9 (1.8 to 3.7)
RCC (n=19,0,19)	4.4 (2.1 to 11.1)	999 (999 to 999)	3.0 (1.6 to 3.9)
Mesothelioma (n=41,0,16)	5.5 (3.5 to 6.4)	999 (999 to 999)	3.4 (1.8 to 3.8)
TNBC (n=21,21,14)	1.9 (1.5 to 3.5)	1.8 (1.4 to 2.6)	1.7 (1.3 to 3.4)

No statistical analyses for this end point

Secondary: Phase 2: Progression-free survival (PFS) per irRC

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End point title

Phase 2: Progression-free survival (PFS) per irRC ^[536]

End point description

PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment and the assessment criteria was irRC. PFS is reported by tumor type. Due to EudraCT system limitations, data fields cannot be blank if the number of subjects analyzed in the corresponding column is greater than 0. Therefore, missing values (eg. values when n=0 in the corresponding row) and not available values due to insufficient number of patients with events are indicated as ‘999’.

End point type

Secondary

End point timeframe

From start of treatment to first documented progression or death due to any cause, assessed up to 2.6 years

Notes
[536] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint refers to Phase 2 only.

End point values	Phase 2: Naive - LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive - LAG525 600 mg Q4W + PDR001 400 mg Q4W	Phase 2: Pre-treated - LAG525 400 mg Q3W + PDR001 300 mg Q3W
Number of subjects analysed	121	21	93
Units: months
median (confidence interval 90%)
NSCLC (n=20,0,22)	4.2 (1.7 to 7.4)	999 (999 to 999)	3.5 (1.9 to 4.9)
Melanoma (n=20,0,22)	5.4 (1.6 to 5.6)	999 (999 to 999)	1.9 (1.8 to 3.7)
RCC (n=19,0,19)	5.8 (4.4 to 11.1)	999 (999 to 999)	3.0 (1.6 to 3.9)
Mesothelioma (n=41,0,16)	5.6 (3.5 to 7.4)	999 (999 to 999)	3.4 (1.8 to 5.7)
TNBC (n=21,21,14)	1.9 (1.5 to 3.8)	1.9 (1.4 to 3.6)	1.7 (1.3 to 3.4)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study treatment until last dose of study treatment plus 30 days, up to maximum 4.5 years (phase 1) and 2.7 years (phase 2).

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.1

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W

Reporting group description

Single-agent LAG525 1 mg/kg Q2W (ROW patients)

Reporting group title

Phase 1: LAG525 3 mg/kg Q2W

Reporting group description

Single-agent LAG525 3 mg/kg Q2W

Reporting group title

Phase 1: LAG525 15 mg/kg Q2W

Reporting group description

Single-agent LAG525 15 mg/kg Q2W

Reporting group title

Phase 1: LAG525 240 mg Q2W

Reporting group description

Single-agent LAG525 240 mg Q2W (ROW patients)

Reporting group title

Phase 1: LAG525 400 mg Q2W

Reporting group description

Single-agent LAG525 400 mg Q2W (ROW patients)

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W-JP

Reporting group description

Single-agent LAG525 1 mg/kg Q2W (Japanese patients)

Reporting group title

Phase 1: LAG525 240 mg Q2W-JP

Reporting group description

Single-agent LAG525 240 mg Q2W (Japanese patients)

Reporting group title

Phase 1: LAG525 10 mg/kg Q2W

Reporting group description

Single-agent LAG525 10 mg/kg Q2W

Reporting group title

Phase 1: LAG525 5 mg/kg Q2W

Reporting group description

Single-agent LAG525 5 mg/kg Q2W

Reporting group title

Phase 1: LAG525 400 mg Q2W-JP

Reporting group description

Single-agent LAG525 400 mg Q2W (Japanese patients)

Reporting group title

Phase 1: LAG525 5 mg/kg Q4W

Reporting group description

Single-agent LAG525 5 mg/kg Q4W

Reporting group title

Phase 1: LAG525 3 mg/kg Q4W

Reporting group description

Single-agent LAG525 3 mg/kg Q4W

Reporting group title

Phase 1: LAG525 10 mg/kg Q4W‌

Reporting group description

Single-agent LAG525 10 mg/kg Q4W

Reporting group title

Phase 1: LAG525 400 mg Q4W

Reporting group description

Single-agent LAG525 400 mg Q4W

Reporting group title

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 0.3 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Reporting group description

Combination LAG525 1 mg/kg + PDR001 1 mg/kg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 80 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 240 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q2W/Q2W)

Reporting group title

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 240 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 2: Naive–Melanoma - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with melanoma naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive–NSCLC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with NSCLC naïve to anti-PD-1/PD-L1

Reporting group title

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 300 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 240 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 400 mg (Q2W/Q4W)

Reporting group title

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 1000 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 800 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Reporting group description

Combination LAG525 400 mg + PDR001 400 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Reporting group description

Combination LAG525 80 mg + PDR001 240 mg (Q4W/Q4W)

Reporting group title

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Reporting group description

Combination LAG525 600 mg + PDR001 300 mg (Q3W/Q3W)

Reporting group title

Phase 2: Pre-treated–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with mesothelioma pre-treated with anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated–RCC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with RCC pre-treated with anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated–Melanoma - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with melanoma pre-treated with anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated–NSCLC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with NSCLC pre-treated with anti-PD-1/PD-L1

Reporting group title

All patients

Reporting group description

All patients

Reporting group title

Phase 2: Naive–TNBC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with TNBC naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with mesothelioma naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive–RCC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with RCC naïve to anti-PD-1/PD-L1

Reporting group title

Phase 2: Pre-treated–TNBC - LAG525+PDR001 (Q3W/Q3W)

Reporting group description

Combination LAG525 400 mg + PDR001 300 mg (Q3W/Q3W) in patients with TNBC pre-treated with anti-PD-1/PD-L1

Reporting group title

Phase 2: Naive–TNBC - LAG525+PDR001 (Q4W/Q4W)

Reporting group description

Combination LAG525 600 mg + PDR001 400 mg (Q4W/Q4W) in patients with TNBC naïve to anti-PD-1/PD-L1

Phase 1: LAG525 1 mg/kg Q2W

Phase 1: LAG525 3 mg/kg Q2W

Phase 1: LAG525 15 mg/kg Q2W

Phase 1: LAG525 240 mg Q2W

Phase 1: LAG525 400 mg Q2W

Phase 1: LAG525 1 mg/kg Q2W-JP

Phase 1: LAG525 240 mg Q2W-JP

Phase 1: LAG525 10 mg/kg Q2W

Phase 1: LAG525 5 mg/kg Q2W

Phase 1: LAG525 400 mg Q2W-JP

Phase 1: LAG525 5 mg/kg Q4W

Phase 1: LAG525 3 mg/kg Q4W

Phase 1: LAG525 10 mg/kg Q4W‌

Phase 1: LAG525 400 mg Q4W

Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W

Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W

Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W

Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W

Phase 2: Naive–Melanoma - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Naive–NSCLC - LAG525+PDR001 (Q3W/Q3W)

Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W

Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W

Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W

Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W

Phase 2: Pre-treated–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Pre-treated–RCC - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Pre-treated–Melanoma - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Pre-treated–NSCLC - LAG525+PDR001 (Q3W/Q3W)

All patients

Phase 2: Naive–TNBC - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Naive–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Naive–RCC - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Pre-treated–TNBC - LAG525+PDR001 (Q3W/Q3W)

Phase 2: Naive–TNBC - LAG525+PDR001 (Q4W/Q4W)

Total subjects affected by serious adverse events

subjects affected / exposed

4 / 13 (30.77%)

2 / 12 (16.67%)

3 / 6 (50.00%)

10 / 25 (40.00%)

11 / 24 (45.83%)

0 / 4 (0.00%)

2 / 5 (40.00%)

2 / 6 (33.33%)

5 / 6 (83.33%)

0 / 6 (0.00%)

4 / 6 (66.67%)

2 / 5 (40.00%)

5 / 11 (45.45%)

2 / 5 (40.00%)

3 / 6 (50.00%)

2 / 6 (33.33%)

3 / 6 (50.00%)

1 / 6 (16.67%)

3 / 5 (60.00%)

9 / 20 (45.00%)

3 / 6 (50.00%)

8 / 20 (40.00%)

13 / 20 (65.00%)

4 / 6 (66.67%)

5 / 11 (45.45%)

2 / 6 (33.33%)

5 / 12 (41.67%)

5 / 6 (83.33%)

4 / 7 (57.14%)

6 / 12 (50.00%)

4 / 16 (25.00%)

5 / 19 (26.32%)

8 / 22 (36.36%)

7 / 22 (31.82%)

208 / 490 (42.45%)

9 / 21 (42.86%)

15 / 41 (36.59%)

14 / 19 (73.68%)

4 / 14 (28.57%)

10 / 21 (47.62%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Breast cancer

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cancer pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

2 / 6 (33.33%)

0 / 5 (0.00%)

1 / 11 (9.09%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

6 / 490 (1.22%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 7

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant ascites

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Malignant pleural effusion

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metastases to bone

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Metastases to central nervous system

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oncologic complication

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Synovial sarcoma

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Tumour pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Hypertension

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

1 / 6 (16.67%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

4 / 490 (0.82%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Superior vena cava occlusion

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Vena cava thrombosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

3 / 490 (0.61%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

1 / 14 (7.14%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 3

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Fatigue

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

2 / 25 (8.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 5 (20.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

8 / 490 (1.63%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

2 / 8

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Malaise

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

4 / 490 (0.82%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Peripheral swelling

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

1 / 11 (9.09%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

2 / 20 (10.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

2 / 6 (33.33%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

13 / 490 (2.65%)

1 / 21 (4.76%)

2 / 41 (4.88%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

1 / 2

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

2 / 14

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Systemic inflammatory response syndrome

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Reproductive system and breast disorders

Benign prostatic hyperplasia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Vaginal haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cough

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Dyspnoea

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

2 / 24 (8.33%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

2 / 6 (33.33%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

1 / 12 (8.33%)

2 / 16 (12.50%)

2 / 19 (10.53%)

0 / 22 (0.00%)

20 / 490 (4.08%)

1 / 21 (4.76%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

3 / 21 (14.29%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 22

0 / 1

0 / 2

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Dyspnoea exertional

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

2 / 20 (10.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

12 / 490 (2.45%)

1 / 21 (4.76%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

2 / 21 (9.52%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 15

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

6 / 490 (1.22%)

0 / 21 (0.00%)

1 / 41 (2.44%)

2 / 19 (10.53%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

2 / 6

0 / 0

1 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Pneumothorax

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

4 / 490 (0.82%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Mental status changes

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Product issues

Device occlusion

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Investigations

Amylase increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Blood creatine phosphokinase increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lipase increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Troponin I increased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Urine output decreased

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Injury, poisoning and procedural complications

Clavicle fracture

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Fall

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Femoral neck fracture

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Gastroenteritis radiation

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Pelvic fracture

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Post procedural haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cardiac tamponade

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Coronary artery disease

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Sinus tachycardia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Nervous system disorders

Brain oedema

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cerebral haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Cerebrovascular accident

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Dizziness

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Myasthenia gravis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorder

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Parkinson's disease

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Partial seizures

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Seizure

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Spinal cord compression

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

2 / 20 (10.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 16 (6.25%)

1 / 19 (5.26%)

0 / 22 (0.00%)

3 / 490 (0.61%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Leukocytosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Eye disorders

Eyelid ptosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Visual impairment

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal distension

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

2 / 11 (18.18%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

9 / 490 (1.84%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 10

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Ascites

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

7 / 490 (1.43%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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 / 3

0 / 0

0 / 9

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Colitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 20 (10.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

4 / 490 (0.82%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

0 / 1

0 / 0

2 / 4

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

1 / 13 (7.69%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

3 / 490 (0.61%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

2 / 6 (33.33%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

6 / 490 (1.22%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

5 / 7

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Diverticulum intestinal haemorrhagic

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Duodenal ulcer

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrooesophageal reflux disease

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Ileal ulcer

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Intra-abdominal fluid collection

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestinal obstruction

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Melaena

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

1 / 6 (16.67%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

7 / 490 (1.43%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

2 / 7

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Obstruction gastric

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Pancreatitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

1 / 14 (7.14%)

0 / 21 (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

Pancreatitis acute

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Small intestinal haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Small intestinal obstruction

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

2 / 5 (40.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

5 / 490 (1.02%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subileus

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

9 / 490 (1.84%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 1

0 / 0

1 / 1

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

3 / 9

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Hepatobiliary disorders

Autoimmune hepatitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bile duct stenosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cholangitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cholecystitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

1 / 14 (7.14%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic failure

subjects affected / exposed

0 / 13 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Hepatic haemorrhage

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Hyperbilirubinaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Jaundice

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Liver injury

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Skin and subcutaneous tissue disorders

Dermatitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Ecchymosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

8 / 490 (1.63%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 8

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

Haematuria

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Renal colic

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Renal impairment

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Renal pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Adrenal insufficiency

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypophysitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypothyroidism

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

4 / 490 (0.82%)

1 / 21 (4.76%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 4

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

5 / 490 (1.02%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bone lesion

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Chest wall mass

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Groin pain

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Muscular weakness

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

3 / 490 (0.61%)

0 / 21 (0.00%)

2 / 41 (4.88%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Neck pain

subjects affected / exposed

1 / 13 (7.69%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 20 (5.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

5 / 490 (1.02%)

0 / 21 (0.00%)

1 / 41 (2.44%)

0 / 19 (0.00%)

0 / 14 (0.00%)

1 / 21 (4.76%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pain in jaw

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Pathological fracture

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (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

Polyarthritis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Abscess

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Bacteraemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Bacterial infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchiolitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cellulitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

1 / 21 (4.76%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Clostridium difficile colitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Device related infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

3 / 490 (0.61%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

1 / 14 (7.14%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Escherichia bacteraemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatitis E

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Herpes zoster

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Influenza

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Osteomyelitis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Parainfluenzae virus infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

1 / 16 (6.25%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Pelvic infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

7 / 490 (1.43%)

0 / 21 (0.00%)

1 / 41 (2.44%)

3 / 19 (15.79%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 8

0 / 0

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia viral

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Post procedural infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 7 (14.29%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Rotavirus infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

1 / 22 (4.55%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Sepsis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

6 / 490 (1.22%)

0 / 21 (0.00%)

0 / 41 (0.00%)

1 / 19 (5.26%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 6

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Septic shock

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Soft tissue infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Wound infection

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Adult failure to thrive

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Cachexia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Decreased appetite

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

1 / 25 (4.00%)

1 / 24 (4.17%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 22 (4.55%)

4 / 490 (0.82%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

1 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Diabetic ketoacidosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypercalcaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 12 (8.33%)

0 / 16 (0.00%)

1 / 19 (5.26%)

0 / 22 (0.00%)

5 / 490 (1.02%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

1 / 20 (5.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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

Hypokalaemia

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (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 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 11 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolic acidosis

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

1 / 490 (0.20%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tumour lysis syndrome

subjects affected / exposed

0 / 13 (0.00%)

0 / 12 (0.00%)

1 / 6 (16.67%)

0 / 25 (0.00%)

0 / 24 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 11 (9.09%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 20 (0.00%)

0 / 6 (0.00%)

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 12 (0.00%)

0 / 16 (0.00%)

0 / 19 (0.00%)

0 / 22 (0.00%)

2 / 490 (0.41%)

0 / 21 (0.00%)

0 / 41 (0.00%)

0 / 19 (0.00%)

0 / 14 (0.00%)

0 / 21 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

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

Non-serious adverse events	Phase 1: LAG525 1 mg/kg Q2W	Phase 1: LAG525 3 mg/kg Q2W	Phase 1: LAG525 15 mg/kg Q2W	Phase 1: LAG525 240 mg Q2W	Phase 1: LAG525 400 mg Q2W	Phase 1: LAG525 1 mg/kg Q2W-JP	Phase 1: LAG525 240 mg Q2W-JP	Phase 1: LAG525 10 mg/kg Q2W	Phase 1: LAG525 5 mg/kg Q2W	Phase 1: LAG525 400 mg Q2W-JP	Phase 1: LAG525 5 mg/kg Q4W	Phase 1: LAG525 3 mg/kg Q4W	Phase 1: LAG525 10 mg/kg Q4W‌	Phase 1: LAG525 400 mg Q4W	Phase 1: LAG525 0.3 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 1 mg/kg Q2W + PDR001 1 mg/kg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 80 mg Q2W	Phase 1: LAG525 240 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 80 mg Q2W + PDR001 240 mg Q2W	Phase 1: LAG525 240 mg Q3W + PDR001 300 mg Q3W	Phase 1: LAG525 400 mg Q3W + PDR001 300 mg Q3W	Phase 2: Naive–Melanoma - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Naive–NSCLC - LAG525+PDR001 (Q3W/Q3W)	Phase 1: LAG525 300 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 240 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q2W + PDR001 400 mg Q4W	Phase 1: LAG525 1000 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 800 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 400 mg Q4W + PDR001 400 mg Q4W	Phase 1: LAG525 80 mg Q4W + PDR001 240 mg Q4W	Phase 1: LAG525 600 mg Q3W + PDR001 300 mg Q3W	Phase 2: Pre-treated–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Pre-treated–RCC - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Pre-treated–Melanoma - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Pre-treated–NSCLC - LAG525+PDR001 (Q3W/Q3W)	All patients	Phase 2: Naive–TNBC - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Naive–Mesothelioma - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Naive–RCC - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Pre-treated–TNBC - LAG525+PDR001 (Q3W/Q3W)	Phase 2: Naive–TNBC - LAG525+PDR001 (Q4W/Q4W)
Total subjects affected by non serious adverse events
subjects affected / exposed	13 / 13 (100.00%)	11 / 12 (91.67%)	6 / 6 (100.00%)	24 / 25 (96.00%)	24 / 24 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	11 / 11 (100.00%)	5 / 5 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	19 / 20 (95.00%)	5 / 6 (83.33%)	17 / 20 (85.00%)	19 / 20 (95.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	11 / 11 (100.00%)	6 / 6 (100.00%)	12 / 12 (100.00%)	6 / 6 (100.00%)	7 / 7 (100.00%)	12 / 12 (100.00%)	16 / 16 (100.00%)	19 / 19 (100.00%)	22 / 22 (100.00%)	21 / 22 (95.45%)	481 / 490 (98.16%)	21 / 21 (100.00%)	41 / 41 (100.00%)	19 / 19 (100.00%)	14 / 14 (100.00%)	21 / 21 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	8 / 490 (1.63%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	0	1	0	0	0	2	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	9	0	0	2	0	1
Tumour associated fever
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	2 / 21 (9.52%)
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	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	2
Tumour haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Tumour pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	3 / 16 (18.75%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	11 / 490 (2.24%)	0 / 21 (0.00%)	4 / 41 (9.76%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	2	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	0	0	4	0	0	0	12	0	4	0	1	0
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
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	1	0	0	0	0	0	0	0	0	0	0	4	0	0	1	0	1
Embolism
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	5	0	0	0	1	0
Flushing
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	8 / 490 (1.63%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	1	9	0	3	0	0	0
Haematoma
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Hot flush
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	0	0	0	0	0	1	0	4	1	0	0	0	0
Hypertension
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	3 / 25 (12.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 5 (20.00%)	4 / 20 (20.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	2 / 22 (9.09%)	34 / 490 (6.94%)	5 / 21 (23.81%)	4 / 41 (9.76%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	2	0	4	0	0	0	0	1	0	0	0	0	0	0	1	1	5	1	5	1	0	1	0	3	0	0	0	0	0	2	0	0	3	2	46	7	6	1	0	0
Hypotension
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	3 / 11 (27.27%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	3 / 6 (50.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 22 (4.55%)	22 / 490 (4.49%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	2	1	0	0	0	0	0	0	1	0	3	0	2	0	0	0	0	2	0	0	1	0	0	2	3	0	0	0	1	0	1	1	1	22	0	1	0	0	0
Lymphoedema
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	7 / 490 (1.43%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	2 / 21 (9.52%)
occurrences all number	0	1	0	1	2	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	0	0	0	0	0	8	0	0	0	0	3
Orthostatic hypotension
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0
Peripheral venous disease
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Superior vena cava syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Thrombophlebitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 25 (8.00%)	6 / 24 (25.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 5 (20.00%)	4 / 20 (20.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	0 / 20 (0.00%)	3 / 6 (50.00%)	1 / 6 (16.67%)	3 / 11 (27.27%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 6 (16.67%)	2 / 7 (28.57%)	1 / 12 (8.33%)	1 / 16 (6.25%)	3 / 19 (15.79%)	3 / 22 (13.64%)	5 / 22 (22.73%)	63 / 490 (12.86%)	1 / 21 (4.76%)	9 / 41 (21.95%)	1 / 19 (5.26%)	2 / 14 (14.29%)	3 / 21 (14.29%)
occurrences all number	0	1	0	2	6	0	0	0	1	0	0	0	1	2	0	0	1	1	1	5	1	1	0	4	1	3	0	5	1	2	1	2	3	4	5	72	1	10	1	3	3
Axillary pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Catheter site erythema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Catheter site pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Chest discomfort
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	1	0	0	1	0	0	0	0	0	1	0	0	0	6	0	1	0	0	0
Chills
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	10 / 490 (2.04%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	4	1	1	1	0	1	0	1	1	0	14	0	0	0	0	0
Early satiety
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	2	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Extravasation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Face oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0
Facial pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	3	0	1	0	0	0
Fatigue
subjects affected / exposed	1 / 13 (7.69%)	3 / 12 (25.00%)	3 / 6 (50.00%)	7 / 25 (28.00%)	8 / 24 (33.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 5 (60.00%)	4 / 11 (36.36%)	0 / 5 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	3 / 5 (60.00%)	10 / 20 (50.00%)	1 / 6 (16.67%)	4 / 20 (20.00%)	4 / 20 (20.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 11 (18.18%)	2 / 6 (33.33%)	2 / 12 (16.67%)	2 / 6 (33.33%)	1 / 7 (14.29%)	5 / 12 (41.67%)	8 / 16 (50.00%)	6 / 19 (31.58%)	4 / 22 (18.18%)	2 / 22 (9.09%)	127 / 490 (25.92%)	4 / 21 (19.05%)	9 / 41 (21.95%)	3 / 19 (15.79%)	3 / 14 (21.43%)	6 / 21 (28.57%)
occurrences all number	1	3	3	7	8	0	0	3	2	0	1	3	4	0	2	2	3	2	3	11	1	4	5	2	2	2	3	2	3	1	5	9	6	7	2	137	4	9	3	3	6
Gait disturbance
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Inflammation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	9 / 490 (1.84%)	1 / 21 (4.76%)	2 / 41 (4.88%)	2 / 19 (10.53%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	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	0	0	1	0	0	0	10	1	2	3	0	1
Injection site reaction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Localised oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	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	0	3	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	9 / 490 (1.84%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0	0	2	0	0	0	0	0	10	0	0	1	0	0
Mucosal disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Mucosal dryness
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Nodule
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	2	0	3	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 11 (27.27%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	3 / 12 (25.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	29 / 490 (5.92%)	1 / 21 (4.76%)	6 / 41 (14.63%)	1 / 19 (5.26%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	1	0	0	2	1	0	0	0	0	0	0	0	3	0	0	0	1	0	0	1	0	0	2	0	0	0	0	7	0	1	1	1	0	1	1	33	1	6	1	1	1
Oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	1	4	0	0	1	0	0
Oedema peripheral
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	3 / 6 (50.00%)	0 / 5 (0.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	3 / 20 (15.00%)	1 / 20 (5.00%)	2 / 6 (33.33%)	3 / 6 (50.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	3 / 12 (25.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	1 / 19 (5.26%)	1 / 22 (4.55%)	2 / 22 (9.09%)	47 / 490 (9.59%)	0 / 21 (0.00%)	2 / 41 (4.88%)	4 / 19 (21.05%)	0 / 14 (0.00%)	2 / 21 (9.52%)
occurrences all number	1	1	0	1	1	1	1	0	1	1	1	1	1	0	0	0	0	3	0	2	1	3	1	2	3	3	0	3	0	0	1	2	1	1	2	47	0	2	4	0	2
Pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	23 / 490 (4.69%)	2 / 21 (9.52%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	4 / 21 (19.05%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	1	2	0	1	0	1	0	1	0	1	0	1	2	0	0	0	1	23	2	3	0	0	4
Peripheral swelling
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	11 / 490 (2.24%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	1	1	0	1	11	1	1	0	0	0
Pyrexia
subjects affected / exposed	3 / 13 (23.08%)	0 / 12 (0.00%)	1 / 6 (16.67%)	7 / 25 (28.00%)	5 / 24 (20.83%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 11 (18.18%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 5 (40.00%)	2 / 20 (10.00%)	3 / 6 (50.00%)	3 / 20 (15.00%)	4 / 20 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	2 / 12 (16.67%)	3 / 6 (50.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	5 / 19 (26.32%)	2 / 22 (9.09%)	4 / 22 (18.18%)	85 / 490 (17.35%)	5 / 21 (23.81%)	7 / 41 (17.07%)	4 / 19 (21.05%)	1 / 14 (7.14%)	5 / 21 (23.81%)
occurrences all number	3	0	2	8	7	0	1	0	0	0	1	2	3	2	1	0	2	1	2	5	4	4	5	0	0	7	1	3	4	0	1	5	6	3	4	116	8	9	5	1	6
Secretion discharge
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Suprapubic pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	1	0	0	0	0	0	0	2	0	0	0	0	0
Xerosis
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Immune system disorders
Contrast media allergy
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Reproductive system and breast disorders
Adnexa uteri pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Benign prostatic hyperplasia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Breast haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Breast pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	3 / 21 (14.29%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	1	0	0	0	0	0	5	3	0	0	0	0
Erectile dysfunction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Genital swelling
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Gynaecomastia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Metrorrhagia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Oedema genital
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pelvic pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	2 / 21 (9.52%)
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	0	0	0	0	2	0	0	0	0	0	0	5	0	0	0	1	2
Penile erythema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Penile oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	2	0	0	0	0	0
Scrotal oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Testicular pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Vaginal discharge
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	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	0	0	0	0	0	0	2	0	0	0	0	0
Vulvovaginal pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Aphonia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Bronchial obstruction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Catarrh
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	8 / 490 (1.63%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	1	1	0	0	0	0	2	0	14	0	8	0	0	0
Cough
subjects affected / exposed	2 / 13 (15.38%)	1 / 12 (8.33%)	2 / 6 (33.33%)	3 / 25 (12.00%)	5 / 24 (20.83%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	4 / 11 (36.36%)	2 / 5 (40.00%)	4 / 6 (66.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 5 (20.00%)	3 / 20 (15.00%)	1 / 6 (16.67%)	3 / 20 (15.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 11 (27.27%)	1 / 6 (16.67%)	3 / 12 (25.00%)	3 / 6 (50.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	3 / 16 (18.75%)	5 / 19 (26.32%)	3 / 22 (13.64%)	3 / 22 (13.64%)	94 / 490 (19.18%)	3 / 21 (14.29%)	11 / 41 (26.83%)	5 / 19 (26.32%)	3 / 14 (21.43%)	4 / 21 (19.05%)
occurrences all number	2	1	2	3	6	0	0	0	1	0	0	1	4	2	5	1	1	3	1	3	1	3	3	0	1	4	1	5	4	0	2	4	5	3	3	103	3	13	5	3	4
Dysphonia
subjects affected / exposed	2 / 13 (15.38%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	11 / 490 (2.24%)	1 / 21 (4.76%)	1 / 41 (2.44%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	0	1	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	0	0	0	0	0	0	2	11	1	1	2	0	0
Dyspnoea
subjects affected / exposed	3 / 13 (23.08%)	0 / 12 (0.00%)	2 / 6 (33.33%)	4 / 25 (16.00%)	7 / 24 (29.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 11 (27.27%)	1 / 5 (20.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	6 / 20 (30.00%)	1 / 6 (16.67%)	3 / 20 (15.00%)	4 / 20 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	4 / 11 (36.36%)	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 6 (33.33%)	0 / 7 (0.00%)	1 / 12 (8.33%)	8 / 16 (50.00%)	2 / 19 (10.53%)	2 / 22 (9.09%)	3 / 22 (13.64%)	95 / 490 (19.39%)	2 / 21 (9.52%)	7 / 41 (17.07%)	5 / 19 (26.32%)	3 / 14 (21.43%)	5 / 21 (23.81%)
occurrences all number	3	0	2	4	7	0	1	1	2	0	1	1	3	1	2	1	3	1	1	8	1	3	6	0	1	5	1	1	2	0	1	8	2	2	3	101	2	8	5	3	5
Dyspnoea exertional
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	14 / 490 (2.86%)	1 / 21 (4.76%)	2 / 41 (4.88%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0	1	0	1	0	0	1	0	0	0	0	14	1	2	1	1	0
Epistaxis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0
Haemoptysis
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	3 / 22 (13.64%)	17 / 490 (3.47%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	1	2	1	0	0	1	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	1	3	18	0	1	1	0	1
Hiccups
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	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	0	0	0	0	0	0	2	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	5	0	0	0	0	0
Interstitial lung disease
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	1	3	0	0	0	1	0
Nasal congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	10 / 490 (2.04%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	2	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	11	1	1	0	0	0
Nasal dryness
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Nasal polyps
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	16 / 490 (3.27%)	2 / 21 (9.52%)	0 / 41 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	1	3	0	0	0	0	1	0	0	0	1	0	2	0	1	0	1	0	0	1	0	1	18	2	0	1	1	0
Pleural effusion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	2 / 20 (10.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	16 / 490 (3.27%)	1 / 21 (4.76%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	1	0	1	0	0	0	0	1	0	1	0	2	3	0	0	0	0	0	0	0	0	1	0	0	2	17	1	0	2	0	0
Pleuritic pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	3	0	1	0	0	0
Pneumonitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	4	0	2	0	0	0
Pneumothorax
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	0	0	0	0	0	0	1	3	0	0	0	0	0
Productive cough
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	4 / 20 (20.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	5 / 22 (22.73%)	20 / 490 (4.08%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	2	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	5	1	0	1	0	0	0	1	0	0	0	1	5	22	0	1	1	0	0
Pulmonary embolism
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	4	0	0	0	0	0
Respiratory depression
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	2	0	0	0	0	0	0	0	0	0	0	5	0	0	1	0	0
Rhinorrhoea
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	12 / 490 (2.45%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	2 / 21 (9.52%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	0	0	0	1	1	0	1	0	0	2	1	13	0	0	1	0	2
Sinus congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	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	0	0	0	0	0	0	0	3	0	0	0	0	0
Sneezing
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Tachypnoea
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
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	0	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1
Tonsillar disorder
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Upper respiratory tract congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	1	1	0	0	5	0	1	0	0	0
Wheezing
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	3	0	0	0	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	21 / 490 (4.29%)	0 / 21 (0.00%)	3 / 41 (7.32%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	1	0	1	1	0	1	0	0	0	0	0	1	0	0	0	0	2	0	1	0	0	0	0	1	0	1	1	0	0	1	2	0	0	2	21	0	3	1	0	1
Confusional state
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	3	0	1	0	0	0
Depression
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	7 / 490 (1.43%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	1	1	0	1	8	0	3	0	0	0
Hallucination
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hallucination, visual
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Insomnia
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	6 / 24 (25.00%)	2 / 4 (50.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 11 (9.09%)	1 / 6 (16.67%)	2 / 12 (16.67%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	36 / 490 (7.35%)	2 / 21 (9.52%)	3 / 41 (7.32%)	2 / 19 (10.53%)	2 / 14 (14.29%)	1 / 21 (4.76%)
occurrences all number	1	0	0	1	6	3	0	0	0	2	0	0	1	0	1	0	0	0	0	0	0	1	0	1	1	1	1	2	1	0	1	3	0	1	0	38	2	3	2	2	1
Irritability
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Personality change
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Sleep disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 13 (7.69%)	2 / 12 (16.67%)	1 / 6 (16.67%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 16 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	1 / 22 (4.55%)	34 / 490 (6.94%)	1 / 21 (4.76%)	1 / 41 (2.44%)	2 / 19 (10.53%)	2 / 14 (14.29%)	1 / 21 (4.76%)
occurrences all number	1	2	1	2	1	0	0	0	0	1	0	0	0	0	4	0	0	0	0	4	0	1	2	1	0	0	1	2	0	0	3	0	2	1	1	37	1	1	2	2	1
Amylase increased
subjects affected / exposed	2 / 13 (15.38%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	2 / 19 (10.53%)	0 / 22 (0.00%)	0 / 22 (0.00%)	24 / 490 (4.90%)	0 / 21 (0.00%)	3 / 41 (7.32%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	2	1	0	2	1	0	0	0	1	1	0	0	0	0	0	0	0	1	0	2	1	0	1	0	0	2	0	0	2	0	0	0	3	0	0	30	0	8	1	1	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 13 (7.69%)	2 / 12 (16.67%)	1 / 6 (16.67%)	2 / 25 (8.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	2 / 20 (10.00%)	3 / 20 (15.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 12 (25.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	40 / 490 (8.16%)	1 / 21 (4.76%)	2 / 41 (4.88%)	2 / 19 (10.53%)	1 / 14 (7.14%)	2 / 21 (9.52%)
occurrences all number	1	2	1	2	2	0	0	0	0	1	0	0	1	0	4	0	0	1	0	4	0	2	3	1	0	0	3	2	0	0	4	0	1	1	0	44	1	2	2	1	2
Blood albumin decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	3	0	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	2 / 13 (15.38%)	1 / 12 (8.33%)	0 / 6 (0.00%)	4 / 25 (16.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	29 / 490 (5.92%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	2	1	0	4	2	0	0	0	0	0	0	0	1	0	1	0	0	1	1	3	0	2	0	1	0	3	1	3	0	1	2	0	0	1	0	33	0	1	1	1	0
Blood bilirubin increased
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	3 / 25 (12.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	17 / 490 (3.47%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	1	0	3	2	0	0	0	1	1	0	0	1	1	0	0	0	0	0	1	0	0	0	1	0	0	2	0	0	0	0	0	1	0	0	17	0	0	1	0	1
Blood calcium
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Blood creatinine increased
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 22 (4.55%)	26 / 490 (5.31%)	1 / 21 (4.76%)	2 / 41 (4.88%)	3 / 19 (15.79%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	2	1	1	1	0	0	0	1	0	0	0	2	0	1	0	0	1	0	0	1	1	1	1	1	0	0	1	0	0	0	0	1	1	1	26	1	2	3	1	0
Blood glucose increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood potassium increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Blood prolactin abnormal
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood sodium decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	4	0	0	0	0	0
Blood thyroid stimulating hormone abnormal
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	1	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Blood urea increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	1	0	4	0	1	0	0	0
Blood uric acid increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	2	0	0	0	0	0
C-reactive protein increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	1	0	0	0	2	0	0	0	0	0
Computerised tomogram abnormal
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	7 / 490 (1.43%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0	0	0	0	0	0	2	0	0	0	0	7	0	0	0	0	0
Glomerular filtration rate decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haemoglobin decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	1	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	0	0	0	0	0	8	0	4	0	0	1
Hepatitis C virus test positive
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lipase increased
subjects affected / exposed	2 / 13 (15.38%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	3 / 24 (12.50%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	1 / 19 (5.26%)	0 / 22 (0.00%)	2 / 22 (9.09%)	27 / 490 (5.51%)	1 / 21 (4.76%)	3 / 41 (7.32%)	1 / 19 (5.26%)	2 / 14 (14.29%)	0 / 21 (0.00%)
occurrences all number	2	0	0	1	3	0	0	0	1	1	0	0	0	0	0	0	1	1	0	2	2	0	0	1	0	1	0	0	1	0	0	2	3	0	2	37	1	8	2	2	0
Lymphocyte count decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	13 / 490 (2.65%)	2 / 21 (9.52%)	2 / 41 (4.88%)	2 / 19 (10.53%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	1	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	1	1	0	16	2	2	5	1	1
Lymphocyte count increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Neutrophil count decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	2	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	0	1	0	4	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	7 / 490 (1.43%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	1	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	0	0	0	0	7	0	1	1	0	0
Protein urine
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Thyroxine free abnormal
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Transaminases increased
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	2	0	0	0	0	0	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	0	0	0	3	0	0	0	0	0
Urine output decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Weight decreased
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	5 / 20 (25.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	30 / 490 (6.12%)	0 / 21 (0.00%)	3 / 41 (7.32%)	4 / 19 (21.05%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	1	1	1	0	0	2	0	0	0	2	1	0	1	0	0	0	0	5	0	1	3	0	0	1	0	0	0	0	1	2	0	0	1	32	0	3	4	0	1
Weight increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	6	0	0	1	0	0
White blood cell count
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
White blood cell count decreased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	3 / 5 (60.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	9 / 490 (1.84%)	2 / 21 (9.52%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	1	5	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	0	1	0	13	2	0	3	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	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	0	0	0	0	0	0	0	7	0	0	2	0	0
Eye contusion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Hand fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0
Head injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0	0
Ligament sprain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Limb injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lumbar vertebral fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	1	2	0	0	0	0	0
Poisoning
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Post procedural inflammation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Postoperative wound complication
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Procedural nausea
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Procedural pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	9 / 490 (1.84%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0	0	1	0	1	1	0	0	0	9	0	0	0	0	0
Spinal compression fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Sunburn
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Wound haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cardiac disorders
Aortic valve disease
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Atrial flutter
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Atrial tachycardia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Atrioventricular block first degree
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	5	1	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	5 / 490 (1.02%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	2	5	0	1	0	0	0
Sinus bradycardia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	0	0	0	0	2	0	1	0	0	0
Sinus tachycardia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	8 / 490 (1.63%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	2	0	0	0	0	0	0	0	1	0	0	0	0	1	1	0	0	0	0	0	1	0	0	1	9	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
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	0	0	0	2	0	0	0	1	0	0	0	0	0	5	0	0	0	0	1
Ventricular arrhythmia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Ventricular tachycardia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Nervous system disorders
Amnesia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Ataxia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Brain oedema
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	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	0	0	0	0	3	0	0	0	0	0
Clonus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cognitive disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Dizziness
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	28 / 490 (5.71%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	4 / 21 (19.05%)
occurrences all number	1	0	1	0	1	0	0	0	1	0	0	0	0	0	2	1	0	0	0	1	0	1	3	0	0	2	1	1	1	1	1	4	0	1	0	30	0	2	0	0	4
Dysgeusia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	15 / 490 (3.06%)	0 / 21 (0.00%)	4 / 41 (9.76%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	1	1	0	0	0	1	2	1	1	0	0	16	0	4	0	0	0
Dyskinesia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Essential tremor
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Facial paralysis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Headache
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	0 / 6 (0.00%)	3 / 25 (12.00%)	5 / 24 (20.83%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	2 / 12 (16.67%)	1 / 6 (16.67%)	2 / 7 (28.57%)	0 / 12 (0.00%)	3 / 16 (18.75%)	5 / 19 (26.32%)	6 / 22 (27.27%)	2 / 22 (9.09%)	56 / 490 (11.43%)	2 / 21 (9.52%)	3 / 41 (7.32%)	0 / 19 (0.00%)	2 / 14 (14.29%)	2 / 21 (9.52%)
occurrences all number	1	1	0	3	6	0	0	0	0	0	1	0	1	0	0	1	2	1	2	2	4	1	2	2	0	2	1	8	1	2	0	6	5	7	4	78	2	5	0	3	2
Hemiparesis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	2	0	1	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	1	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	0	0	0	0	0	4	0	0	1	0	0
Lethargy
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	2	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Neuropathy peripheral
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	7 / 490 (1.43%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	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	1	0	0	0	0	1	0	0	1	8	0	0	0	0	2
Paraesthesia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 22 (0.00%)	14 / 490 (2.86%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	1	1	5	0	0	0	0	0	2	0	0	0	0	0	1	0	2	0	16	0	1	1	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	1	0	0	0	0	0	0	0	0	0	1	0	0	4	0	0	0	0	0
Polyneuropathy
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	1	0	2	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	5 / 490 (1.02%)	2 / 21 (9.52%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	5	2	0	1	0	0
Seizure
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Somnolence
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	3 / 19 (15.79%)	0 / 22 (0.00%)	0 / 22 (0.00%)	8 / 490 (1.63%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	3	0	0	8	0	1	0	0	0
Spinal cord compression
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	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	0	0	0	1	0	1	5	0	0	1	0	0
Tremor
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	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	1	0	0	1	0	6	0	1	0	0	0
Trigeminal nerve disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	3 / 13 (23.08%)	3 / 12 (25.00%)	2 / 6 (33.33%)	3 / 25 (12.00%)	6 / 24 (25.00%)	2 / 4 (50.00%)	3 / 5 (60.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	3 / 6 (50.00%)	1 / 5 (20.00%)	3 / 11 (27.27%)	0 / 5 (0.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 5 (20.00%)	5 / 20 (25.00%)	1 / 6 (16.67%)	2 / 20 (10.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	4 / 11 (36.36%)	1 / 6 (16.67%)	2 / 12 (16.67%)	2 / 6 (33.33%)	2 / 7 (28.57%)	2 / 12 (16.67%)	1 / 16 (6.25%)	4 / 19 (21.05%)	6 / 22 (27.27%)	1 / 22 (4.55%)	92 / 490 (18.78%)	2 / 21 (9.52%)	3 / 41 (7.32%)	9 / 19 (47.37%)	0 / 14 (0.00%)	3 / 21 (14.29%)
occurrences all number	3	3	2	4	7	2	4	2	2	0	3	3	3	0	3	1	1	0	2	7	1	2	2	1	1	4	2	2	3	2	2	1	4	6	3	111	2	6	12	0	3
Disseminated intravascular coagulation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	2	0	0	0	3	0	1	0	0	0
Leukocytosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	0	0	0	1	0	0	0	3	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	1	0	0	0	0	1	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	0	0	4	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	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	0	0	0	0	0	0	0	0	3	0	0	0	0	0
Lymphopenia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
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	0	0	0	0	0	0	0	0	2	0	0	3	0	0	0	0	1
Neutropenia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	8 / 490 (1.63%)	1 / 21 (4.76%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	1	3	0	0	0	9	1	2	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	11 / 490 (2.24%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	2 / 14 (14.29%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	1	2	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	1	12	1	1	0	2	0
Thrombocytosis
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Ear and labyrinth disorders
Ear congestion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Ear pain
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	0	0	0	1	0	0	0	4	1	0	0	0	0
External ear disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypoacusis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	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	0	0	0	1	0	0	3	0	0	0	0	0
Otorrhoea
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Vertigo
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0
Eye disorders
Blepharitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	2	0	1	0	0	0
Blindness unilateral
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Diplopia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Dry eye
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	1	0	0	0	1	0	0	0	4	1	0	0	0	0
Erythema of eyelid
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eye oedema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Eye pruritus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	0	4	0	2	0	0	0
Eye swelling
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eyelid ptosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	1	0	0
Keratitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Lacrimal disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Lacrimation increased
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	5 / 490 (1.02%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	2	0	1	0	0	0	2	0	7	1	1	0	0	0
Periorbital swelling
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Swelling of eyelid
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Vision blurred
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 22 (0.00%)	14 / 490 (2.86%)	2 / 21 (9.52%)	1 / 41 (2.44%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	2	1	0	0	1	0	1	0	0	0	2	0	2	0	16	2	1	0	2	0
Visual acuity reduced
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vitreous floaters
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	4	0	6	0	0	1	0	0
Abdominal distension
subjects affected / exposed	0 / 13 (0.00%)	4 / 12 (33.33%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 5 (20.00%)	3 / 11 (27.27%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	4 / 20 (20.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	27 / 490 (5.51%)	0 / 21 (0.00%)	2 / 41 (4.88%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	4	0	2	1	0	0	1	0	1	0	1	3	0	0	0	0	1	0	1	0	4	2	0	1	1	0	0	0	1	0	1	0	0	0	28	0	2	1	0	0
Abdominal hernia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Abdominal pain
subjects affected / exposed	1 / 13 (7.69%)	2 / 12 (16.67%)	1 / 6 (16.67%)	3 / 25 (12.00%)	6 / 24 (25.00%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	2 / 11 (18.18%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 5 (20.00%)	5 / 20 (25.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	3 / 6 (50.00%)	2 / 12 (16.67%)	2 / 6 (33.33%)	1 / 7 (14.29%)	1 / 12 (8.33%)	3 / 16 (18.75%)	2 / 19 (10.53%)	6 / 22 (27.27%)	2 / 22 (9.09%)	68 / 490 (13.88%)	1 / 21 (4.76%)	3 / 41 (7.32%)	3 / 19 (15.79%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	2	2	2	3	7	1	2	1	2	0	1	2	2	2	0	0	1	1	1	7	0	0	1	0	1	2	5	2	2	1	1	4	3	6	2	80	1	5	3	1	1
Abdominal pain lower
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	6	0	0	1	1	0
Abdominal pain upper
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	1 / 22 (4.55%)	2 / 22 (9.09%)	24 / 490 (4.90%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	2	1	0	0	0	0	0	0	0	1	0	1	1	2	2	0	1	0	1	0	0	0	2	0	2	0	3	0	2	0	3	2	30	0	3	0	0	0
Anal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Anal incontinence
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	2	0	0	0	0	0	0	0	3	0	0	0	0	0
Anal pruritus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Aphthous ulcer
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0
Aptyalism
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	0	0	2	0	1	0	0	0
Ascites
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	2 / 20 (10.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	13 / 490 (2.65%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0	0	1	0	0	0	1	2	0	0	1	14	0	0	2	0	0
Colitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	1	0	0	0	3	0	1	0	0	0
Constipation
subjects affected / exposed	3 / 13 (23.08%)	2 / 12 (16.67%)	4 / 6 (66.67%)	3 / 25 (12.00%)	6 / 24 (25.00%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	4 / 11 (36.36%)	1 / 5 (20.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 5 (40.00%)	7 / 20 (35.00%)	0 / 6 (0.00%)	4 / 20 (20.00%)	10 / 20 (50.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	3 / 11 (27.27%)	2 / 6 (33.33%)	3 / 12 (25.00%)	3 / 6 (50.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	0 / 16 (0.00%)	5 / 19 (26.32%)	4 / 22 (18.18%)	3 / 22 (13.64%)	102 / 490 (20.82%)	2 / 21 (9.52%)	7 / 41 (17.07%)	4 / 19 (21.05%)	0 / 14 (0.00%)	4 / 21 (19.05%)
occurrences all number	3	2	4	3	6	2	1	0	2	2	2	1	4	1	2	0	2	0	2	7	0	4	10	1	0	3	2	3	3	1	2	0	5	4	4	107	2	7	6	0	4
Dental caries
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Diarrhoea
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	0 / 6 (0.00%)	5 / 25 (20.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	3 / 6 (50.00%)	1 / 5 (20.00%)	10 / 20 (50.00%)	2 / 6 (33.33%)	4 / 20 (20.00%)	5 / 20 (25.00%)	4 / 6 (66.67%)	0 / 6 (0.00%)	3 / 11 (27.27%)	2 / 6 (33.33%)	6 / 12 (50.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	3 / 12 (25.00%)	4 / 16 (25.00%)	1 / 19 (5.26%)	4 / 22 (18.18%)	5 / 22 (22.73%)	91 / 490 (18.57%)	3 / 21 (14.29%)	8 / 41 (19.51%)	4 / 19 (21.05%)	2 / 14 (14.29%)	2 / 21 (9.52%)
occurrences all number	1	2	0	6	2	0	0	1	1	1	0	0	1	0	0	0	1	5	1	14	2	4	5	8	0	6	6	7	1	0	13	10	1	5	7	146	5	19	5	4	2
Dry mouth
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 24 (4.17%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	1 / 22 (4.55%)	2 / 22 (9.09%)	28 / 490 (5.71%)	1 / 21 (4.76%)	3 / 41 (7.32%)	1 / 19 (5.26%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	3	0	2	1	1	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0	1	2	0	5	0	0	1	0	1	1	0	1	2	32	1	4	1	1	1
Duodenal ulcer
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0	0
Dyspepsia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	3 / 19 (15.79%)	1 / 22 (4.55%)	1 / 22 (4.55%)	16 / 490 (3.27%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0	2	1	0	0	1	3	1	2	18	1	1	0	1	0
Dysphagia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	11 / 490 (2.24%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	2	1	1	0	0	0	0	0	0	0	0	0	1	1	0	1	11	0	0	1	0	0
Epigastric discomfort
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Flatulence
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	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	0	0	3	0	0	0	0	0
Gastric ulcer
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	4 / 12 (33.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	25 / 490 (5.10%)	1 / 21 (4.76%)	3 / 41 (7.32%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	1	1	0	0	0	0	0	1	0	1	0	0	0	0	1	0	3	0	1	0	0	1	0	0	6	1	0	1	2	0	0	1	27	1	3	1	0	0
Gingival bleeding
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	2	0	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Glossitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Haematochezia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	1	0	0
Haemorrhoids
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	7 / 490 (1.43%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	1	7	0	0	1	0	0
Hypoaesthesia oral
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Inguinal hernia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Intra-abdominal fluid collection
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Large intestinal obstruction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Melaena
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	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	0	0	0	0	0	4	0	0	1	0	0
Mouth ulceration
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	1	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	0	0	0	0	0	0	0	0	3	0	0	0	0	1
Nausea
subjects affected / exposed	1 / 13 (7.69%)	3 / 12 (25.00%)	1 / 6 (16.67%)	8 / 25 (32.00%)	7 / 24 (29.17%)	0 / 4 (0.00%)	2 / 5 (40.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 5 (0.00%)	3 / 11 (27.27%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 5 (40.00%)	9 / 20 (45.00%)	2 / 6 (33.33%)	6 / 20 (30.00%)	2 / 20 (10.00%)	3 / 6 (50.00%)	2 / 6 (33.33%)	5 / 11 (45.45%)	1 / 6 (16.67%)	7 / 12 (58.33%)	0 / 6 (0.00%)	3 / 7 (42.86%)	4 / 12 (33.33%)	6 / 16 (37.50%)	3 / 19 (15.79%)	9 / 22 (40.91%)	7 / 22 (31.82%)	134 / 490 (27.35%)	3 / 21 (14.29%)	12 / 41 (29.27%)	5 / 19 (26.32%)	1 / 14 (7.14%)	5 / 21 (23.81%)
occurrences all number	1	3	1	11	7	0	2	2	1	2	2	0	5	1	1	1	2	0	2	13	2	6	2	5	3	9	2	12	0	3	7	9	3	12	8	168	3	13	5	2	5
Odynophagia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	2	0	0	0	0	0	0	0	7	0	4	0	0	0
Oesophagitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	1	1	0	0
Oral pain
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0
Pancreatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	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	3	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	0	0	2	0	0	0	0	0
Rectal tenesmus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Small intestinal obstruction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	4 / 20 (20.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 22 (4.55%)	22 / 490 (4.49%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	0	0	2	0	0	1	0	0	0	0	1	0	0	0	0	0	1	0	5	0	0	1	0	0	0	1	2	0	0	1	2	1	2	1	25	0	2	0	1	1
Tongue discomfort
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	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	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	2	0	6	0	1	0	0	0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0
Vomiting
subjects affected / exposed	1 / 13 (7.69%)	2 / 12 (16.67%)	1 / 6 (16.67%)	5 / 25 (20.00%)	5 / 24 (20.83%)	0 / 4 (0.00%)	2 / 5 (40.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 5 (40.00%)	3 / 20 (15.00%)	2 / 6 (33.33%)	1 / 20 (5.00%)	2 / 20 (10.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	4 / 11 (36.36%)	0 / 6 (0.00%)	4 / 12 (33.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	4 / 12 (33.33%)	1 / 16 (6.25%)	2 / 19 (10.53%)	4 / 22 (18.18%)	6 / 22 (27.27%)	85 / 490 (17.35%)	3 / 21 (14.29%)	5 / 41 (12.20%)	5 / 19 (26.32%)	1 / 14 (7.14%)	5 / 21 (23.81%)
occurrences all number	1	2	1	7	5	0	2	1	1	1	3	1	4	0	2	0	1	2	2	3	2	1	2	2	2	5	0	6	0	1	5	1	2	4	8	102	3	6	6	1	6
Hepatobiliary disorders
Bile duct stenosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cholecystitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	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	0	0	0	2	0	0	0	0	0
Cholelithiasis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Hepatic pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hepatic vein thrombosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Hyperbilirubinaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6	0	0	0	0	0
Hypertransaminasaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Jaundice
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	2	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	1	0
Ocular icterus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dermatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	1	0	0	0	0	0	0	0	4	1	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0	0
Dry skin
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	3 / 20 (15.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	1 / 22 (4.55%)	2 / 22 (9.09%)	24 / 490 (4.90%)	1 / 21 (4.76%)	2 / 41 (4.88%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	2	0	1	2	0	0	1	0	2	0	0	1	0	0	0	1	1	0	0	0	1	3	2	0	0	0	0	0	0	0	1	0	2	3	27	1	2	1	0	0
Ecchymosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	1	0
Eczema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	1 / 21 (4.76%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	7	3	1	1	0	0
Erythema
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	9 / 490 (1.84%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	2	0	0	0	1	0	2	0	0	0	0	0	0	0	0	0	10	0	0	0	1	1
Haemorrhage subcutaneous
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	1	0	0	0	4	1	0	0	0	0
Nail disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	1	0	0	0	0	0	0	0	3	0	0	0	0	0
Nail toxicity
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Night sweats
subjects affected / exposed	2 / 13 (15.38%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	7 / 490 (1.43%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	2	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	1	7	0	0	0	0	0
Onychoclasis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0
Papule
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	2	1	0	0	0	0
Pruritus
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 20 (15.00%)	1 / 6 (16.67%)	2 / 20 (10.00%)	4 / 20 (20.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	4 / 16 (25.00%)	1 / 19 (5.26%)	3 / 22 (13.64%)	1 / 22 (4.55%)	64 / 490 (13.06%)	7 / 21 (33.33%)	8 / 41 (19.51%)	3 / 19 (15.79%)	3 / 14 (21.43%)	5 / 21 (23.81%)
occurrences all number	0	2	1	1	2	0	1	0	0	1	1	0	1	1	1	1	1	0	0	3	1	3	5	1	0	2	1	1	0	1	0	5	1	3	1	78	12	11	3	4	6
Rash
subjects affected / exposed	2 / 13 (15.38%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 5 (0.00%)	5 / 20 (25.00%)	1 / 6 (16.67%)	5 / 20 (25.00%)	5 / 20 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 12 (8.33%)	4 / 16 (25.00%)	3 / 19 (15.79%)	5 / 22 (22.73%)	4 / 22 (18.18%)	57 / 490 (11.63%)	1 / 21 (4.76%)	2 / 41 (4.88%)	7 / 19 (36.84%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	2	0	0	0	2	0	0	1	1	0	1	0	0	0	0	0	1	1	0	7	1	6	5	0	0	1	0	2	0	1	1	5	3	6	6	68	3	2	9	0	1
Rash macular
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	0	0	0	0	0	0	4	2	1	0	0	0
Rash maculo-papular
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	3 / 6 (50.00%)	2 / 6 (33.33%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	24 / 490 (4.90%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	1	0	4	2	1	0	1	2	1	1	3	0	2	1	0	1	0	0	0	2	0	1	1	27	0	1	0	0	1
Rash pruritic
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	10 / 490 (2.04%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	2	0	0	2	0	2	4	0	1	0	0	0	0	17	0	4	0	0	0
Skin exfoliation
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Skin lesion
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	4	0	2	0	0	0
Skin mass
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0
Skin ulcer
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0
Urticaria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Vitiligo
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	3 / 20 (15.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	2 / 22 (9.09%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	3	0	0	0	0	0	0	0	0	0	1	0	3	0	7	0	0	0	0	0
Xeroderma
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	10 / 490 (2.04%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	1	2	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	0	0	1	0	0	0	10	0	0	1	0	0
Bladder disorder
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Chronic kidney disease
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Dysuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	8 / 490 (1.63%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	4	0	0	1	0	0	0	0	1	0	10	0	3	0	0	0
Haematuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	10 / 490 (2.04%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	1	1	4	3	0	0	0	1	0	16	0	0	1	0	0
Hydronephrosis
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Micturition urgency
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	2	0	0	0	0	0
Nocturia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	1	0	2	0	0	0	0	0
Oliguria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	1	0
Pollakiuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	1	0	0	0	0	0	0	1	0	0	0	0	4	0	0	0	0	0
Proteinuria
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Renal failure
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	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	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Renal impairment
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0
Renal pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0
Urinary incontinence
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	1	0	0	1	0	0	0	0	4	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	1	1	4	0	0	0	0	0
Urinary tract obstruction
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	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	0	3	0	0	0	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	1	3	0	0	1	0	0
Hyperthyroidism
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	16 / 490 (3.27%)	2 / 21 (9.52%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	1	1	1	0	0	0	0	0	0	0	0	2	0	0	0	16	2	3	0	0	1
Hypophysitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	36 / 490 (7.35%)	1 / 21 (4.76%)	5 / 41 (12.20%)	4 / 19 (21.05%)	1 / 14 (7.14%)	1 / 21 (4.76%)
occurrences all number	0	2	1	1	0	1	0	0	0	0	0	1	0	0	1	2	3	2	0	1	0	2	2	1	0	1	0	1	0	1	0	3	2	1	0	41	1	5	4	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	3 / 13 (23.08%)	1 / 12 (8.33%)	1 / 6 (16.67%)	4 / 25 (16.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	1 / 5 (20.00%)	4 / 20 (20.00%)	1 / 6 (16.67%)	4 / 20 (20.00%)	7 / 20 (35.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 11 (18.18%)	2 / 6 (33.33%)	4 / 12 (33.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	2 / 12 (16.67%)	4 / 16 (25.00%)	1 / 19 (5.26%)	7 / 22 (31.82%)	4 / 22 (18.18%)	88 / 490 (17.96%)	6 / 21 (28.57%)	8 / 41 (19.51%)	5 / 19 (26.32%)	1 / 14 (7.14%)	3 / 21 (14.29%)
occurrences all number	4	1	1	4	2	0	0	1	1	0	0	1	2	0	2	0	0	2	1	9	2	4	9	1	1	4	3	5	0	1	2	5	1	14	5	114	6	8	8	1	3
Arthritis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	1	1	0	4	0	0	0	0	0
Autoimmune arthritis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Back pain
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	2 / 6 (33.33%)	2 / 25 (8.00%)	4 / 24 (16.67%)	0 / 4 (0.00%)	4 / 5 (80.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 20 (15.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	4 / 11 (36.36%)	2 / 6 (33.33%)	3 / 12 (25.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	3 / 16 (18.75%)	1 / 19 (5.26%)	5 / 22 (22.73%)	4 / 22 (18.18%)	69 / 490 (14.08%)	1 / 21 (4.76%)	6 / 41 (14.63%)	3 / 19 (15.79%)	1 / 14 (7.14%)	2 / 21 (9.52%)
occurrences all number	1	1	2	2	4	0	4	1	1	0	1	0	2	0	0	1	0	1	1	3	1	1	3	0	2	7	2	3	0	0	2	3	1	6	4	75	1	6	4	2	2
Bone pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	13 / 490 (2.65%)	1 / 21 (4.76%)	2 / 41 (4.88%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	2	0	0	0	0	0	0	0	2	0	0	0	2	14	1	2	0	1	0
Flank pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	10 / 490 (2.04%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	1	1	1	0	10	0	2	0	0	0
Groin pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	2 / 22 (9.09%)	1 / 22 (4.55%)	9 / 490 (1.84%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	1	2	1	9	1	1	0	0	0
Intervertebral disc displacement
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Joint stiffness
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Joint swelling
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	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	0	0	1	0	0	0	0	3	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	11 / 490 (2.24%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	4	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	14	0	3	0	1	0
Muscular weakness
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	14 / 490 (2.86%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	1	2	0	1	1	0	0	0	0	1	0	0	0	1	0	0	1	0	0	3	0	1	0	0	15	0	1	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	2 / 19 (10.53%)	1 / 22 (4.55%)	2 / 22 (9.09%)	20 / 490 (4.08%)	0 / 21 (0.00%)	4 / 41 (9.76%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	1	0	1	1	0	0	1	0	0	0	1	0	0	0	0	1	1	0	1	0	3	1	3	22	0	4	1	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	3	0	1	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	2	0	1	0	0	0
Myalgia
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	2 / 6 (33.33%)	1 / 25 (4.00%)	4 / 24 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 5 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	2 / 6 (33.33%)	0 / 6 (0.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	2 / 16 (12.50%)	1 / 19 (5.26%)	0 / 22 (0.00%)	3 / 22 (13.64%)	36 / 490 (7.35%)	3 / 21 (14.29%)	1 / 41 (2.44%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	2	2	1	5	0	0	0	0	0	0	0	1	0	0	1	1	2	0	2	0	0	0	5	0	3	0	1	0	0	2	2	1	0	3	41	3	1	1	2	0
Neck pain
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	0 / 22 (0.00%)	11 / 490 (2.24%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	1	0	0	1	0	0	1	0	0	0	1	0	0	1	1	0	11	0	2	0	0	1
Pain in extremity
subjects affected / exposed	1 / 13 (7.69%)	1 / 12 (8.33%)	0 / 6 (0.00%)	3 / 25 (12.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	2 / 20 (10.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	0 / 7 (0.00%)	1 / 12 (8.33%)	2 / 16 (12.50%)	0 / 19 (0.00%)	2 / 22 (9.09%)	2 / 22 (9.09%)	34 / 490 (6.94%)	1 / 21 (4.76%)	4 / 41 (9.76%)	0 / 19 (0.00%)	0 / 14 (0.00%)	2 / 21 (9.52%)
occurrences all number	1	1	0	3	1	0	1	0	0	0	0	0	1	0	1	1	1	0	0	1	0	2	2	0	0	2	0	0	2	0	1	2	0	2	2	35	1	4	0	0	3
Pain in jaw
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	1	0	0	1	1	1	0	0	6	0	0	0	0	0
Pathological fracture
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Polyarthritis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	3	0	0	0	0	0	0	0	0	1	0	0	0	0	5	0	0	0	0	0
Tendonitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	3	0	1	0	0	0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Bronchitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	1	1	0	0	0	0	0	0	0	0	0	0	1	0	6	0	1	1	0	0
Candida infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	1 / 22 (4.55%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	5	0	0	0	0	0
Clostridium difficile colitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Clostridium difficile infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	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	0	0	1	0	0	0	0	0	0	3	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	0	0	3	0	1	0	0	0
Device related infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Ear infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	2 / 22 (9.09%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	2	0	4	0	1	0	0	0
Erythema migrans
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Escherichia urinary tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Gingivitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hepatitis B
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Herpes dermatitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Herpes zoster
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	1	0	0	3	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Influenza
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	14 / 490 (2.86%)	1 / 21 (4.76%)	1 / 41 (2.44%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	0	1	0	1	0	0	0	0	1	1	0	1	0	0	2	1	0	1	1	0	0	0	15	1	1	1	0	0
Infusion site infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 12 (8.33%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	1	0	1	0	0	0	0	4	0	1	0	0	0
Mucosal infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	8 / 490 (1.63%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	1	0	0	0	0	0	1	0	0	0	8	0	1	0	0	1
Oral candidiasis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	1 / 22 (4.55%)	8 / 490 (1.63%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	2	0	1	1	0	0	0	0	0	0	0	1	9	0	1	0	0	0
Oral herpes
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 22 (4.55%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	3	0	0	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	1	1	7	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	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	0	3	0	0	0	0	0
Paronychia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	3	0	0
Pharyngitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	1	0	0	4	0	0	2	0	0
Pneumonia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	16 / 490 (3.27%)	0 / 21 (0.00%)	3 / 41 (7.32%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	1	0	2	0	2	0	0	0	2	0	0	0	0	0	2	17	0	3	0	0	0
Pneumonia bacterial
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Post procedural infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	2	0	1	0	0	1	0	0	6	0	2	0	0	0
Respiratory tract infection viral
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (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	0	2	0	0	0	0	0	0	1	0	0	0	5	0	0	2	0	0
Sepsis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	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	0	0	0	0	0	0	2	0	0	0	0	0
Sialoadenitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	1 / 21 (4.76%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	3	1	1	0	0	0
Sinusitis
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	3	0	0	0	0	0	0	0	0	1	0	0	5	0	0	0	0	0
Skin infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	5 / 490 (1.02%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	5	0	0	0	0	0
Tinea infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Tinea versicolour
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Tooth abscess
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	2	0	0	0	0	0	0	0	3	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	2 / 25 (8.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	2 / 22 (9.09%)	3 / 22 (13.64%)	25 / 490 (5.10%)	0 / 21 (0.00%)	6 / 41 (14.63%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	1	2	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	3	0	0	2	0	0	0	0	2	0	0	0	1	0	2	3	25	0	6	1	1	0
Urinary tract infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 11 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 20 (10.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	2 / 22 (9.09%)	18 / 490 (3.67%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	1 / 21 (4.76%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	1	0	0	1	1	0	0	0	0	3	1	0	2	0	1	1	0	0	0	0	1	2	0	0	3	21	0	0	1	0	1
Viral infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	1	0	1	1	0	0	3	0	0	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	0	0	0	0	0	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	0	0	0	2	0	0	0	0	0
Wound infection
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	1 / 21 (4.76%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	1	0	0	0	0
Metabolism and nutrition disorders
Cachexia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0
Decreased appetite
subjects affected / exposed	3 / 13 (23.08%)	3 / 12 (25.00%)	2 / 6 (33.33%)	6 / 25 (24.00%)	6 / 24 (25.00%)	0 / 4 (0.00%)	3 / 5 (60.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 11 (9.09%)	3 / 5 (60.00%)	3 / 6 (50.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 5 (40.00%)	9 / 20 (45.00%)	0 / 6 (0.00%)	2 / 20 (10.00%)	4 / 20 (20.00%)	2 / 6 (33.33%)	2 / 6 (33.33%)	3 / 11 (27.27%)	2 / 6 (33.33%)	3 / 12 (25.00%)	3 / 6 (50.00%)	1 / 7 (14.29%)	6 / 12 (50.00%)	3 / 16 (18.75%)	3 / 19 (15.79%)	5 / 22 (22.73%)	6 / 22 (27.27%)	113 / 490 (23.06%)	4 / 21 (19.05%)	11 / 41 (26.83%)	4 / 19 (21.05%)	1 / 14 (7.14%)	2 / 21 (9.52%)
occurrences all number	3	3	2	6	6	0	5	0	2	2	0	1	1	3	3	0	0	0	3	11	0	2	4	2	2	4	3	3	3	1	7	3	3	5	7	123	4	12	4	1	2
Dehydration
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	1 / 16 (6.25%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	13 / 490 (2.65%)	0 / 21 (0.00%)	1 / 41 (2.44%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	2	0	0	1	2	0	3	1	1	0	0	2	1	0	0	0	17	0	1	0	0	0
Diabetes mellitus
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	2 / 490 (0.41%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	1	0	1	0	0	0	0	0	0	0	2	0	0	0	0	0
Gout
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0	0
Hyperamylasaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypercalcaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	3 / 19 (15.79%)	0 / 22 (0.00%)	0 / 22 (0.00%)	17 / 490 (3.47%)	0 / 21 (0.00%)	1 / 41 (2.44%)	3 / 19 (15.79%)	2 / 14 (14.29%)	0 / 21 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	2	0	0	0	0	0	0	0	1	0	0	2	0	3	0	0	0	0	3	0	0	23	0	1	5	4	0
Hyperglycaemia
subjects affected / exposed	0 / 13 (0.00%)	3 / 12 (25.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	1 / 6 (16.67%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	2 / 22 (9.09%)	18 / 490 (3.67%)	1 / 21 (4.76%)	2 / 41 (4.88%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	3	1	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	1	0	1	2	1	0	0	1	0	2	20	1	3	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 13 (0.00%)	2 / 12 (16.67%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	2 / 16 (12.50%)	4 / 19 (21.05%)	1 / 22 (4.55%)	0 / 22 (0.00%)	22 / 490 (4.49%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	3 / 14 (21.43%)	0 / 21 (0.00%)
occurrences all number	0	2	1	2	1	0	0	0	0	0	0	1	2	0	0	0	0	0	0	0	0	1	0	0	0	0	0	4	0	0	0	2	5	1	0	28	0	0	2	4	0
Hypermagnesaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0
Hypernatraemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	1 / 20 (5.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	3 / 490 (0.61%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	1	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	2	0
Hyperphosphataemia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	6 / 490 (1.22%)	0 / 21 (0.00%)	0 / 41 (0.00%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	2	1	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	0	0	0	0	0	0	7	0	0	2	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	4 / 490 (0.82%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	1	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	0	4	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 13 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 12 (16.67%)	1 / 16 (6.25%)	1 / 19 (5.26%)	1 / 22 (4.55%)	1 / 22 (4.55%)	22 / 490 (4.49%)	1 / 21 (4.76%)	2 / 41 (4.88%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	0	0	0	0	1	0	1	1	0	1	1	4	0	0	1	0	1	1	0	0	0	0	2	3	1	1	1	27	1	2	1	0	0
Hypocalcaemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 24 (4.17%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	1 / 19 (5.26%)	0 / 22 (0.00%)	0 / 22 (0.00%)	9 / 490 (1.84%)	2 / 21 (9.52%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	9	2	0	1	0	0
Hypokalaemia
subjects affected / exposed	3 / 13 (23.08%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 6 (33.33%)	0 / 5 (0.00%)	3 / 20 (15.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	3 / 12 (25.00%)	1 / 16 (6.25%)	0 / 19 (0.00%)	1 / 22 (4.55%)	1 / 22 (4.55%)	25 / 490 (5.10%)	1 / 21 (4.76%)	2 / 41 (4.88%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	3	1	0	0	2	0	0	0	1	0	0	0	0	0	1	0	0	3	0	6	0	0	1	0	0	1	0	0	0	0	3	1	0	1	1	29	1	2	1	0	0
Hypomagnesaemia
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	2 / 24 (8.33%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 11 (9.09%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	2 / 20 (10.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	1 / 19 (5.26%)	0 / 22 (0.00%)	1 / 22 (4.55%)	23 / 490 (4.69%)	0 / 21 (0.00%)	1 / 41 (2.44%)	1 / 19 (5.26%)	1 / 14 (7.14%)	2 / 21 (9.52%)
occurrences all number	1	0	1	2	2	0	0	0	1	0	1	0	3	0	1	0	0	0	0	1	0	0	3	0	0	2	0	2	0	0	0	1	1	0	1	29	0	1	1	2	2
Hyponatraemia
subjects affected / exposed	1 / 13 (7.69%)	0 / 12 (0.00%)	3 / 6 (50.00%)	2 / 25 (8.00%)	3 / 24 (12.50%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	5 / 20 (25.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	1 / 16 (6.25%)	2 / 19 (10.53%)	0 / 22 (0.00%)	0 / 22 (0.00%)	31 / 490 (6.33%)	1 / 21 (4.76%)	3 / 41 (7.32%)	2 / 19 (10.53%)	0 / 14 (0.00%)	0 / 21 (0.00%)
occurrences all number	1	0	3	2	3	0	0	1	0	0	0	0	0	0	0	0	0	4	2	1	0	0	5	0	0	1	1	1	0	0	0	1	4	0	0	42	1	5	6	0	0
Hypophosphataemia
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	4 / 24 (16.67%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 11 (18.18%)	0 / 5 (0.00%)	1 / 6 (16.67%)	2 / 6 (33.33%)	0 / 6 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 20 (5.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	1 / 20 (5.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 12 (8.33%)	1 / 16 (6.25%)	0 / 19 (0.00%)	2 / 22 (9.09%)	1 / 22 (4.55%)	28 / 490 (5.71%)	0 / 21 (0.00%)	4 / 41 (9.76%)	1 / 19 (5.26%)	1 / 14 (7.14%)	0 / 21 (0.00%)
occurrences all number	0	0	0	1	4	0	0	0	1	0	0	0	2	0	1	3	0	1	0	2	0	0	1	2	1	0	1	0	0	0	1	1	0	2	1	34	0	7	1	1	0
Iron deficiency
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	1 / 14 (7.14%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Malnutrition
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	0 / 19 (0.00%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vitamin B1 deficiency
subjects affected / exposed	0 / 13 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 24 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 11 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 20 (0.00%)	0 / 20 (0.00%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 12 (0.00%)	0 / 16 (0.00%)	0 / 19 (0.00%)	0 / 22 (0.00%)	0 / 22 (0.00%)	1 / 490 (0.20%)	0 / 21 (0.00%)	0 / 41 (0.00%)	1 / 19 (5.26%)	0 / 14 (0.00%)	0 / 21 (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	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

17 Apr 2015

Revise the DLT criterion for thrombocytopenia to include CTCAE grade 3 thrombocytopenia with clinically significant bleeding as a DLT as requested by a regulatory authority.

14 Sep 2015

To focus the Phase II dose expansion on three main cancers: NSCLC, melanoma and renal cell carcinoma to determine the efficacy of single-agent LAG525 and the combination of LAG525 with PDR001 in both the PD-1/PD-L1 pre-treated and naive settings; Allow the option to test alternate dosing (i.e. flat dosing) within single-agent dose escalation and/or Phase II expansion if flat dosing is supported by emerging PK data generated during the study. Flat dosing may also be tested in the combination part of the study for both LAG525 and PDR001; Allow the option to test two doses of LAG525 during Phase II expansion; Clarification of certain exclusion criteria, and prohibited concomitant medications; Update text regarding collection of biomarkers samples and newly obtained tumor biopsies; Update safety monitoring/reporting period.

04 Dec 2015

To specify that if required by a Regulatory Authority, recruitment to combination dose levels will begin at dose level -1 (0.3 mg/kg LAG525 with 1 mg/kg PDR001) for patients from those countries; To specify that for the combination arm, the first dose for the first two patients treated at each untested dose level will be staggered by 24 hours.

12 Feb 2016

The purpose of this amendment is to include a Japanese dose escalation arm for single-agent LAG525. The Japanese dose escalation will run separately from the on-going dose escalation with a starting dose for single-agent LAG525 in Japanese patients of 1 mg/kg Q2W. Dose escalation decisions will be guided by a BLRM; In response to the growing number of patients with renal cancer receiving anti-PD-1/PD-L1 therapy, expansion arms have been added for patients with renal cancer who are refractory to or have relapsed following prior treatment with PD-1/PD-L1 inhibitors to explore whether LAG525 alone or in combination with PDR001 can overcome PD-1/PD-L1 resistance; The prohibited concomitant therapy section was updated to allow localized radiotherapy for non-target lesions; Determination of EGFR, ALK, or BRAF V600 status by a local laboratory.

12 Apr 2016

The purpose of this amendment is to incorporate the following modifications of the exclusion criteria requested by a regulatory authority: Exclusion Criteria 02: Revised to exclude patients with history of severe hypersensitivity reactions to study treatment ingredients or other mAbs; Exclusion Criteria 07: Criterion added to exclude patients with a history of drug-induced pneumonitis or current pneumonitis; Exclusion Criteria 23: Clarified the definition of women who are considered postmenopausal and not of child bearing potential.

05 Jul 2016

The protocol is amended to increase the duration of contraception and safety follow-up periods post PDR001 treatment from 90 days to 150 days. These changes are related to an Urgent Safety Measure communicated on 08-June-2016 to all investigators. For logistical simplicity, these changes are applicable for all patients in both the single-agent LAG525 and combination LAG525 + PDR001 study arms.

09 Dec 2016

Added guidance for patients with hyperglycemia or other signs and symptoms of diabetes and diabetic ketoacidosis as requested by regulatory authority; Revise the pharmacodynamic marker sample collection and analysis plan in order to align with other protocols testing PDR001 and to incorporate newly available PD assays to assess pathway modulation.; Some eligibility criteria were updated.

21 Jun 2017

Addition of mesothelioma and TNBC indications in the combination arm of the Phase II part of the study, based on preliminary evidence of anti-tumor activity seen in these indications during the dose-escalation portion of the study; To allow single-agent LAG525 patients to continue study treatment with LAG525 in combination with PDR001 upon disease progression after at least 4 cycles of LAG525 monotherapy treatment and to detail the required tests/samples to be collected; Reduced PK blood sampling time-points in order to minimize the number of blood samples collected for the Phase II patients; Inclusion and exclusion criteria were updated; Best overall response per was changed from 30 to 150 days due to delayed patient response.

16 Aug 2018

The primary purpose of this amendment was to incorporate health authority-requested language requiring study treatment discontinuation in the event of Stevens-Johnson syndrome / toxic epidermal necrolysis. In addition, the protocol was revised to align with recently published guidelines on the clinical management of suspected immune-related toxicities. Other modifications of the protocol included updates on the withdrawal of study consent language, clarification of survival follow-up, clarify language regarding PD in the End of Treatment disposition section, update statistical analysis section to align with objectives and update to irRC guideline.

27 Jul 2019

The primary purpose of this amendment was to revise the definition of ‘end of study’. It was expanded to include the option for patients still on treatment and who, in the opinion of the investigator, were still deriving clinical benefit at the time of end of study, to transfer to another study or to an alternative treatment option to continue providing study treatment to these patients. In addition, the objective/endpoint to assess the pharmacodynamic effect of the single-agent LAG525 and the combination of LAG525 and PDR001 using mRNA was switched from secondary to exploratory as it is hypothesis-generating only. The correlation of PD-L1, LAG3 IHC and efficacy for LAG525 as single-agent and in combination with PDR001 was also switched from secondary to an exploratory objective for the same reason.

Were there any global interruptions to the trial? No

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

Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com for complete trial results.

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Clinical trials

Clinical Trial Results: A Phase I/II, open label, multicenter study of the safety and efficacy of LAG525 single agent and in combination with PDR001 administered to patients with advanced malignancies

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)

Primary: Phase 1: Number of participants with Dose-Limiting Toxicities (DLTs)

Primary: Phase 2: Overall Response Rate (ORR) per RECIST 1.1

Primary: Phase 2: Overall Response Rate (ORR) per RECIST 1.1

Secondary: Phase 1: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Phase 1: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Phase 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Phase 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary: Phase 1: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

Secondary: Phase 1: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

Secondary: Phase 2: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

Secondary: Phase 2: Number of participants with dose reductions and dose interruptions of LAG525 and PDR001

Secondary: Phase 1: Relative dose intensity (RDI) of LAG525 and PDR001

Secondary: Phase 1: Relative dose intensity (RDI) of LAG525 and PDR001

Secondary: Phase 2: Relative dose intensity (RDI) of LAG525 and PDR001

Secondary: Phase 2: Relative dose intensity (RDI) of LAG525 and PDR001

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of LAG525

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of LAG525

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of LAG525

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of LAG525

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of LAG525

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of LAG525

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of LAG525

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of LAG525

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of LAG525

Secondary: Phase 1: Terminal elimination half-life (T1/2) of LAG525

Secondary: Phase 1: Terminal elimination half-life (T1/2) of LAG525

Secondary: Phase 2: Terminal elimination half-life (T1/2) of LAG525

Secondary: Phase 2: Terminal elimination half-life (T1/2) of LAG525

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of PDR001

Secondary: Phase 1: Maximum observed serum concentration (Cmax) of PDR001

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of PDR001

Secondary: Phase 2: Maximum observed serum concentration (Cmax) of PDR001

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of PDR001

Secondary: Phase 1: Time to reach maximum serum concentration (Tmax) of PDR001

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of PDR001

Secondary: Phase 2: Time to reach maximum serum concentration (Tmax) of PDR001

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

Secondary: Phase 1: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

Secondary: Phase 2: Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001

Secondary: Phase 1: Terminal elimination half-life (T1/2) of PDR001

Secondary: Phase 1: Terminal elimination half-life (T1/2) of PDR001

Secondary: Phase 2: Terminal elimination half-life (T1/2) of PDR001

Secondary: Phase 2: Terminal elimination half-life (T1/2) of PDR001

Secondary: Phase 1: Number of participants with anti-LAG525 antibodies

Secondary: Phase 1: Number of participants with anti-LAG525 antibodies

Secondary: Phase 2: Number of participants with anti-LAG525 antibodies

Secondary: Phase 2: Number of participants with anti-LAG525 antibodies

Secondary: Phase 1: Number of participants with anti-PDR001 antibodies

Secondary: Phase 1: Number of participants with anti-PDR001 antibodies

Secondary: Phase 2: Number of participants with anti-PDR001 antibodies

Secondary: Phase 2: Number of participants with anti-PDR001 antibodies

Secondary: Phase 1: Overall Response Rate (ORR) per RECIST 1.1

Secondary: Phase 1: Overall Response Rate (ORR) per RECIST 1.1

Secondary: Phase 1: Overall Response Rate (ORR) per irRC

Secondary: Phase 1: Overall Response Rate (ORR) per irRC

Secondary: Phase 2: Overall Response Rate (ORR) per irRC

Secondary: Phase 2: Overall Response Rate (ORR) per irRC

Secondary: Phase 1: Disease Control Rate (DCR) per RECIST 1.1

Secondary: Phase 1: Disease Control Rate (DCR) per RECIST 1.1

Secondary: Phase 1: Disease Control Rate (DCR) per irRC

Secondary: Phase 1: Disease Control Rate (DCR) per irRC

Secondary: Phase 2: Disease Control Rate (DCR) per RECIST 1.1

Secondary: Phase 2: Disease Control Rate (DCR) per RECIST 1.1

Secondary: Phase 2: Disease Control Rate (DCR) per irRC

Secondary: Phase 2: Disease Control Rate (DCR) per irRC

Clinical Trial Results:
A Phase I/II, open label, multicenter study of the safety and efficacy of LAG525 single agent and in combination with PDR001 administered to patients with advanced malignancies