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Clinical Trial Results:
Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

Summary
EudraCT number	2013-004810-16
Trial protocol	GB ES DE NL PT
Global end of trial date	22 Oct 2024

Results information
Results version number	v1(current)
This version publication date	02 Nov 2025
First version publication date	02 Nov 2025
Other versions

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

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Trial information

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Sponsor protocol code

TPU-TAS-120-101

ISRCTN number

US NCT number

NCT02052778

WHO universal trial number (UTN)

Sponsor organisation name

Taiho Oncology, Inc.

Sponsor organisation address

101 Carnegie Center, Suite 101, Princeton, New Jersey, United States, 08540

Public contact

Senior Study Manager, Taiho Oncology, Inc, +1 844-878-2446, medicalinformation@taihooncology.com

Scientific contact

Senior Study Manager, Taiho Oncology, Inc., +1 844-878-2446, medicalinformation@taihooncology.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

29 May 2021

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

22 Oct 2024

Was the trial ended prematurely?

Main objective of the trial

The primary objectives of the trial were: Phase 1 Dose Escalation: to determine the maximum tolerated dose (MTD) and/or Recommended Phase 2 dose (RP2D) of TAS-120. Phase 1 Expansion: to further evaluate the efficacy and safety of the MTD and/or RP2D of TAS-120 in subjects with tumors harboring specific Fibroblast growth factor/ Fibroblast growth factor receptor (FGF/FGFR) aberrations. Phase 2: to confirm the Objective Response Rate (ORR) of TAS-120 in Intra-hepatic cholangiocarcinoma (iCCA) patients with tumors harboring FGFR2 gene fusions or other FGFR2 rearrangements.

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form (ICF).

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Jul 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 3

Country: Number of subjects enrolled

Australia: 16

Country: Number of subjects enrolled

Korea, Republic of: 19

Country: Number of subjects enrolled

United States: 166

Country: Number of subjects enrolled

Canada: 1

Country: Number of subjects enrolled

Japan: 14

Country: Number of subjects enrolled

Taiwan: 6

Country: Number of subjects enrolled

Hong Kong: 1

Country: Number of subjects enrolled

Spain: 42

Country: Number of subjects enrolled

United Kingdom: 46

Country: Number of subjects enrolled

France: 69

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Italy: 2

Worldwide total number of subjects

386

EEA total number of subjects

117

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)

290

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Study had Phase 1 and 2. Phase 1: Dose Escalation: 86 treated and Dose Expansion: 197 treated; Phase 2: 103 treated. For Subject Disposition, Baseline characteristics, and Adverse Events, QOD and QD dosing were combined for Phase 1 Dose Escalation as pre-planned in protocol.

Screening details

Phase 1 Dose Expansion sub-cohorts 1&2: efficacy data presented at 30-Jun-2019 cut-off as all subjects had disease progression or had discontinued. Primary analysis (PFS&OS) data were presented as pre planned in protocol at this cut-off. Phase 1 Expansion & Phase 2, subjects with clinical benefit had efficacy data presented at 29-May-2021 cut-off.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase 1: Dose Escalation: QOD Dosing: 8 mg

Arm description

Subjects with or without fibroblast growth factor [FGF]/fibroblast growth factor receptor [FGFR] gene abnormalities received TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 16 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received TAS-120 16 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 24 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received TAS-120 24 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 36 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received TAS-120 36 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Capsule, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 56 mg

Arm description

Subjects with FGF/FGFR gene abnormalities received TAS-120 56 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Capsule, Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 80 mg

Arm description

Subjects with FGF/FGFR gene abnormalities received TAS-120 80 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 120 mg

Arm description

Subjects with FGF/FGFR gene abnormalities received TAS-120 120 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 160 mg

Arm description

Subjects with FGF/FGFR gene abnormalities received TAS-120 160 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QOD Dosing: 200 mg

Arm description

Subjects with FGF/FGFR gene abnormalities received TAS-120 200 mg orally QOD (Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 was administered orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle.

Phase 1: Dose Escalation: (Once Daily) QD Dosing: 4 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 4 mg orally once daily (QD) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 4 mg was administered orally once daily (QD) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QD Dosing: 8 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 8 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 8 mg was administered orally once daily (QD) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QD Dosing: 16 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 16 mg was administered orally once daily (QD) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QD Dosing: 20 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 20 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg was administered orally once daily (QD) in a 21-day treatment cycle.

Phase 1: Dose Escalation: QD Dosing: 24 mg

Arm description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 24 mg was administered orally once daily (QD) in a 21-day treatment cycle.

Phase 1: Dose Expansion Cohort 1

Arm description

Subjects with intra-hepatic or extrahepatic cholangiocarcinoma (iCCA or eCCA) harboring FGFR2 gene fusions or rearrangements and who were treated or not treated with prior FGFR inhibitors received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Cohort 2

Arm description

Subjects with primary central nervous system (CNS) tumors harboring FGFR gene fusions or FGFR1 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Cohort 3

Arm description

Subjects with advanced urothelial carcinoma harboring FGFR3 gene fusions or FGFR3 activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Cohort 4

Arm description

Subjects with breast or gastric cancer with harboring FGFR2 amplification received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Cohort 5

Arm description

Subjects with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Cohort 6

Arm description

Subjects who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Sub-cohort 1

Arm description

Subjects with iCCA who were enrolled prior to the confirmation of the recommended Phase 2 dose (RP2D) received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 16 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 1: Dose Expansion: Sub-cohort 2

Arm description

Subjects with other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 16 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Phase 2

Arm description

Subjects with iCCA with tumors harboring FGFR2 gene rearrangements received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Arm type

Experimental

Investigational medicinal product name

Futibatinib

Investigational medicinal product code

TAS-120

Other name

Pharmaceutical forms

Film-coated tablet

Routes of administration

Oral use

Dosage and administration details

TAS-120 20 mg tablets were administered orally daily QD in each of 21-day treatment cycle.

Number of subjects in period 1	Phase 1: Dose Escalation: QOD Dosing: 8 mg	Phase 1: Dose Escalation: QOD Dosing: 16 mg	Phase 1: Dose Escalation: QOD Dosing: 24 mg	Phase 1: Dose Escalation: QOD Dosing: 36 mg	Phase 1: Dose Escalation: QOD Dosing: 56 mg	Phase 1: Dose Escalation: QOD Dosing: 80 mg	Phase 1: Dose Escalation: QOD Dosing: 120 mg	Phase 1: Dose Escalation: QOD Dosing: 160 mg	Phase 1: Dose Escalation: QOD Dosing: 200 mg	Phase 1: Dose Escalation: (Once Daily) QD Dosing: 4 mg	Phase 1: Dose Escalation: QD Dosing: 8 mg	Phase 1: Dose Escalation: QD Dosing: 16 mg	Phase 1: Dose Escalation: QD Dosing: 20 mg	Phase 1: Dose Escalation: QD Dosing: 24 mg	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Sub-cohort 1	Phase 1: Dose Expansion: Sub-cohort 2	Phase 2
Started	6	3	3	3	3	5	4	8	7	4	5	14	7	14	57	34	15	13	24	27	19	8	103
Completed	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	6	3	3	3	3	5	4	8	7	4	5	14	7	14	57	34	15	13	24	27	19	8	103
Adverse Event	-	-	-	-	-	-	-	-	-	-	-	-	-	1	5	1	3	-	3	1	-	-	7
Death	-	-	-	-	-	-	1	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-	-
Clinical disease progression	2	1	1	2	1	1	3	2	1	-	-	2	2	3	6	3	-	2	3	4	5	1	6
Radiographic progression	-	2	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Investigator decision	-	-	-	-	-	1	-	-	-	-	-	-	1	-	5	3	-	-	-	1	-	-	3
Radiographic progression	4	-	2	1	2	3	-	6	5	4	5	11	4	7	38	23	12	11	17	21	14	6	78
Unspecified	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	1	-	-	1	-	-	1	7
Withdrawal by subject	-	-	-	-	-	-	-	-	1	-	-	-	-	3	2	3	-	-	-	-	-	-	2

Baseline characteristics

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Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 8 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 16 mg

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Phase 1: Dose Escalation: QOD Dosing: 24 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 36 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 56 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 80 mg

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Phase 1: Dose Escalation: QOD Dosing: 120 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 160 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 200 mg

Reporting group description

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Phase 1: Dose Escalation: (Once Daily) QD Dosing: 4 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 8 mg

Reporting group description

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Phase 1: Dose Escalation: QD Dosing: 16 mg

Reporting group description

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Phase 1: Dose Escalation: QD Dosing: 20 mg

Reporting group description

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Phase 1: Dose Escalation: QD Dosing: 24 mg

Reporting group description

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Phase 1: Dose Expansion Cohort 1

Reporting group description

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Phase 1: Dose Expansion: Cohort 2

Reporting group description

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Phase 1: Dose Expansion: Cohort 3

Reporting group description

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Phase 1: Dose Expansion: Cohort 4

Reporting group description

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Phase 1: Dose Expansion: Cohort 5

Reporting group description

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Phase 1: Dose Expansion: Cohort 6

Reporting group description

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Phase 1: Dose Expansion: Sub-cohort 1

Reporting group description

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Phase 1: Dose Expansion: Sub-cohort 2

Reporting group description

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Phase 2

Reporting group description

Reporting group values	Phase 1: Dose Escalation: QOD Dosing: 8 mg	Phase 1: Dose Escalation: QOD Dosing: 16 mg	Phase 1: Dose Escalation: QOD Dosing: 24 mg	Phase 1: Dose Escalation: QOD Dosing: 36 mg	Phase 1: Dose Escalation: QOD Dosing: 56 mg	Phase 1: Dose Escalation: QOD Dosing: 80 mg	Phase 1: Dose Escalation: QOD Dosing: 120 mg	Phase 1: Dose Escalation: QOD Dosing: 160 mg	Phase 1: Dose Escalation: QOD Dosing: 200 mg	Phase 1: Dose Escalation: (Once Daily) QD Dosing: 4 mg	Phase 1: Dose Escalation: QD Dosing: 8 mg	Phase 1: Dose Escalation: QD Dosing: 16 mg	Phase 1: Dose Escalation: QD Dosing: 20 mg	Phase 1: Dose Escalation: QD Dosing: 24 mg	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Sub-cohort 1	Phase 1: Dose Expansion: Sub-cohort 2	Phase 2	Total
Number of subjects	6	3	3	3	3	5	4	8	7	4	5	14	7	14	57	34	15	13	24	27	19	8	103	386
Age categorical
Units: Subjects
</=18 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
Between 18 and 65 years	4	2	2	2	2	3	1	6	5	3	3	12	4	11	45	27	5	10	21	18	18	6	80	290
>/=65 years	2	1	1	1	1	2	3	2	2	1	2	2	3	3	12	7	10	3	3	9	1	2	23	96
Gender categorical
Analysis was performed on all treated population.
Units: Subjects
Female	4	1	2	2	0	4	1	4	5	2	0	8	6	13	40	12	4	9	14	16	14	7	58	226
Male	2	2	1	1	3	1	3	4	2	2	5	6	1	1	17	22	11	4	10	11	5	1	45	160
Ethnicity (NIH/OMB)
Analysis was performed on all treated population.
Units: Subjects
Hispanic or Latino	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0	1	1	2	2	9
Not Hispanic or Latino	6	2	3	2	2	2	3	3	3	2	3	7	6	6	41	19	7	13	16	23	18	5	89	281
Unknown or Not Reported	0	1	0	1	1	3	1	5	4	2	2	7	1	7	14	15	8	0	8	3	0	1	12	96
Race/Ethnicity
Units: Subjects
Asian/Oriental	0	0	0	0	0	0	0	0	0	0	0	0	1	2	6	2	0	8	3	2	1	0	30	55
White/Caucasian	6	3	3	3	2	1	3	5	5	3	4	7	6	8	37	17	7	2	15	22	16	7	51	233
Black or African-American	0	0	0	0	0	1	0	0	0	0	1	0	0	0	1	0	0	2	0	1	1	0	8	15
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	2
Missing/Unknown	0	0	0	0	1	3	1	3	2	1	0	7	0	4	13	15	8	0	6	2	1	1	13	81

End points

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Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 8 mg

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Phase 1: Dose Escalation: QOD Dosing: 16 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 24 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 36 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 56 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 80 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 120 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 160 mg

Reporting group description

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Phase 1: Dose Escalation: QOD Dosing: 200 mg

Reporting group description

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Phase 1: Dose Escalation: (Once Daily) QD Dosing: 4 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 8 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 16 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 20 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 24 mg

Reporting group description

Reporting group title

Phase 1: Dose Expansion Cohort 1

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 2

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 3

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 4

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 5

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 6

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Sub-cohort 1

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Sub-cohort 2

Reporting group description

Reporting group title

Phase 2

Reporting group description

Subject analysis set title

Phase 1: Dose Escalation: QOD Dosing

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with or without FGF/FGFR gene abnormalities received TAS-120 at 4 DLs from 8 to 36 mg orally every other day (QOD; Monday, Wednesday and Friday of each week) and subjects with FGF/FGFR abnormalities received TAS-120 at 6 DLs from 56 mg to 240 mg orally QOD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 11 months).

Subject analysis set title

Phase 1: Dose Escalation: QD Dosing

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 4 to 24 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, or any other discontinuation criterion was met (maximum exposure: 24 months).

Subject analysis set title

Phase 1: Dose Expansion: Pooled Sub-cohort

Subject analysis set type

Full analysis

Subject analysis set description

Subjects with iCCA and other tumor types who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Primary: Phase 1: Dose Escalation- MTD

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End point title

Phase 1: Dose Escalation- MTD ^[1]

End point description

MTD: highest dose with <33% DLTs in Cycle 1. DLTs: ≥G3 nonhematologic toxicity; nausea/vomiting >48h despite antiemetics; diarrhea >48h despite antidiarrheals; G4 neutropenia >7d; febrile neutropenia (ANC<1000 & fever ≥38.3°C or ≥38°C >1h); G4/G3 thrombocytopenia with bleeding or transfusion; corneal disorder worsened ≥1 grade; phosphorus ≥9 mg/dL or ≥7 mg/dL ≥7d or requiring phosphate-lowering therapy (PLT) 7d; creatinine >1.5×ULN ≥7d with phosphorus >5.5 mg/dL (PLT 7d) or Ca×P >55 mg/dL (PLT 7d); hypercalcemia G2 >7d or G3; ectopic soft tissue calcification; >G2 toxicities preventing Cycle 1 completion or Cycle 2 start within 2 weeks. ‘9999’-MTD for QOD dosing was not determined as no DLTs were observed for TAS-120 up to 200 mg QOD as the highest dose level studied. DLT evaluable population-all subjects in Phase 1 Dose Escalation who had either experience a DLT during the first cycle of treatment or who had completed the first cycle with at least 80% of planned TAS-120 administered.

End point type

Primary

End point timeframe

Cycle 1 (21-day cycle).

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: Only descriptive statistics is provided for this end point.

End point values	Phase 1: Dose Escalation: QOD Dosing	Phase 1: Dose Escalation: QD Dosing
Number of subjects analysed	42	44
Units: milligrams
number (not applicable)	9999	20

No statistical analyses for this end point

Primary: Phase 1: Dose Escalation- RP2D of TAS-120

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End point title

Phase 1: Dose Escalation- RP2D of TAS-120 ^[2]

End point description

RP2D was MTD or lower. MTD: highest dose with <33% DLTs in Cycle 1. DLTs: ≥G3 nonhematologic toxicity; nausea/vomiting >48h despite antiemetics; diarrhea >48h despite antidiarrheals; G4 neutropenia >7d; febrile neutropenia (ANC<1000 & fever ≥38.3°C or ≥38°C >1h); G4/G3 thrombocytopenia with bleeding or transfusion; corneal disorder worsened ≥1 grade; phosphorus ≥9 mg/dL or ≥7 mg/dL ≥7d or requiring PLT 7d;creatinine >1.5×ULN ≥7d with phosphorus >5.5 mg/dL (PLT 7d) or Ca×P >55 mg/dL (PLT 7d); hypercalcemia G2 >7d or G3; ectopic soft tissue calcification; >G2 toxicities preventing Cycle 1 completion or Cycle 2 start within 2 weeks. ‘9999’-MTD for QOD dosing was not determined as no DLTs were observed for TAS-120 up to 200 mg QOD as the highest dose level studied and thus no RP2D was determined. DLT evaluable population.

End point type

Primary

End point timeframe

Cycle 1 (21-day cycle)

Notes
[2] - 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: Only descriptive statistics is provided for this end point.

End point values	Phase 1: Dose Escalation: QOD Dosing	Phase 1: Dose Escalation: QD Dosing
Number of subjects analysed	42	44
Units: milligrams
number (not applicable)	9999	20

No statistical analyses for this end point

Primary: Phase 1: Dose Expansion: Percentage of Subjects With Objective Response

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End point title

Phase 1: Dose Expansion: Percentage of Subjects With Objective Response ^[3] ^[4]

End point description

Objective response was defined as proportion of subjects who had achieved best overall response of partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 millimeters (mm) and PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions. For Cohorts 1 to 6: Objective response was based on Independent Review Committee (IRC) and for pooled Sub-cohort: Objective response was based on investigator review. Efficacy population included all subjects who had received at least 1 dose of TAS-120. Data was planned to be collected and analysed on pooled population of subjects who received 16 mg of TAS-120 in the sub-cohorts 1and 2.

End point type

Primary

End point timeframe

Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts.

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: Only descriptive statistics is provided for this end point.
[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 outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Pooled Sub-cohort
Number of subjects analysed	57	34	15	13	24	27	27
Units: Percentage of subjects
number (confidence interval 95%)	15.8 (7.5 to 27.9)	8.8 (1.9 to 23.7)	13.3 (1.7 to 40.5)	0 (0.0 to 24.7)	12.5 (2.7 to 32.4)	0 (0.0 to 12.8)	33.3 (16.5 to 54.0)

No statistical analyses for this end point

Primary: Phase 2: Percentage of Subjects With Objective Response

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End point title

Phase 2: Percentage of Subjects With Objective Response ^[5] ^[6]

End point description

Objective response was defined as proportion of subjects who had achieved best overall response of PR or CR per RECIST v1.1. CR was defined as a disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must had reduction in short axis to <10 mm and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. The Phase 2 evaluation of objective response was based on central independent CT/MRI image assessment. Efficacy population included all treated iCCA subjects with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120

End point type

Primary

End point timeframe

Up to approximately 37.5 months (through cut-off date 29-May-2021)

Notes
[5] - 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: Only descriptive statistics is provided for this end point.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	103
Units: Percentage of subjects
number (confidence interval 95%)	41.7 (32.1 to 51.9)

No statistical analyses for this end point

Secondary: Phase 1: Dose Expansion: Duration of Response (DOR)

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End point title

Phase 1: Dose Expansion: Duration of Response (DOR) ^[7]

End point description

A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective progressive disease (PD) or death due to any cause, whichever occurred first. Subjects who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. For Cohorts 1 to 6: DOR was based on IRC and for Group 3, 4, 5, 6 and for pooled Sub-cohort: DOR was based on investigator review. Analysis was performed on the subset of subjects with PR or CR in efficacy population. Here, 'number of subjects analysed' signifies subjects with available data for this outcome measure. Data was planned to be collected and analysed on pooled population of subjects who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.

End point type

Secondary

End point timeframe

Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohorts.

Notes
[7] - 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 outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Pooled Sub-cohort
Number of subjects analysed	9	2	2	0 ^[8]	3	0 ^[9]	9
Units: months
median (full range (min-max))	6.18 (2.8 to 10.6)	3.52 (2.8 to 4.3)	2.45 (1.4 to 3.4)	( to )	2.79 (2.0 to 4.1)	( to )	8.77 (3.5 to 20.8)

Notes
[8] - No subject had an event
[9] - No subject had an event

No statistical analyses for this end point

Secondary: Phase 2: Duration of Response (DOR)

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End point title

Phase 2: Duration of Response (DOR) ^[10]

End point description

A DOR was defined as the time (in months) from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Subjects who started subsequent anticancer therapy without a prior reported progression were censored at the last tumor assessments prior to initiation of the subsequent anticancer therapy. Analysis was performed on the subset of subjects with PR or CR in efficacy population. Here, 'number of subjects analysed' signifies subjects with available data for this outcome measure.

End point type

Secondary

End point timeframe

Up to approximately 37.5 months (through cut-off date 29-May-2021).

Notes
[10] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	43
Units: months
median (full range (min-max))	8.31 (2.1 to 24.8)

No statistical analyses for this end point

Secondary: Phase 1: Dose Expansion: Disease Control Rate (DCR)

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End point title

Phase 1: Dose Expansion: Disease Control Rate (DCR) ^[11]

End point description

DCR was defined as the proportion of subjects with CR, PR, or SD lasting ≥6 weeks after treatment start (no SD confirmation required). CR: disappearance of all target lesions, with lymph nodes <10 mm. PR: ≥30% decrease in sum of target lesion diameters from baseline. SD: neither sufficient shrinkage for PR nor increase for PD, using the smallest on-study sum as reference. For Cohorts 1–6, DCR was per IRC; for pooled sub-cohort, by investigator. Efficacy population included all subjects who had received at least 1 dose of TAS-120. Data was planned to be collected and analysed on pooled population of subjects who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.

End point type

Secondary

End point timeframe

Up to approximately 50.5 months (through cut-off date 29-May-2021) for Cohorts 1 to 6; up to approximately 27.5 months (through cut-off date 30-Jun-2019) for pooled sub-cohort.

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Pooled Sub-cohort
Number of subjects analysed	57	34	15	13	24	27	27
Units: Percentage of subjects
number (confidence interval 95%)	66.7 (52.9 to 78.6)	23.5 (10.7 to 41.2)	33.3 (11.8 to 61.6)	38.5 (13.9 to 68.4)	54.2 (32.8 to 74.4)	22.2 (8.6 to 42.3)	66.7 (46.0 to 83.5)

No statistical analyses for this end point

Secondary: Phase 2: Disease Control Rate (DCR)

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End point title

Phase 2: Disease Control Rate (DCR) ^[12]

End point description

A DCR was defined as the proportion of subjects with objective evidence of CR, PR, or SD, except that there was no requirement for a confirmation of an SD response, if it is maintained for at least 6 weeks post treatment initiation. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes might had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the Baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taken as a reference the smallest sum diameters while on study. DCR was based on IRC. Efficacy population included all treated iCCA subjects with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.

End point type

Secondary

End point timeframe

Up to approximately 37.5 months (through cut-off date 29-May-2021)

Notes
[12] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	103
Units: Percentage of subjects
number (confidence interval 95%)	82.5 (73.8 to 89.3)

No statistical analyses for this end point

Secondary: Phase 1: Dose Expansion: Progression-free Survival (PFS)

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End point title

Phase 1: Dose Expansion: Progression-free Survival (PFS) ^[13]

End point description

PFS was defined as the time (months) from first dose to disease progression or death (any cause), whichever came first. Subjects who died without documented progression were considered progressed at death. Those without progression or death were censored at last tumor assessment; those with no on-study assessment and alive were censored at first dose; and those starting new anti-cancer therapy before progression were censored at last assessment before new therapy. PFS was assessed by IRC for Cohorts 1–6 and by investigator for pooled sub-cohort. Efficacy population included all subjects who had received at least 1 dose of TAS-120. Data was planned to be collected and analysed on pooled population of subjects who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.

End point type

Secondary

End point timeframe

Up to approximately 27.5 months (through cut-off date 30-Jun-2019).

Notes
[13] - 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 outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Pooled Sub-cohort
Number of subjects analysed	57	34	15	13	24	27	27
Units: months
median (confidence interval 95%)	4.1 (2.7 to 6.9)	1.9 (1.3 to 4.9)	1.8 (1.3 to 4.7)	1.3 (0.9 to 4.1)	3.5 (1.7 to 6.8)	2.7 (1.4 to 2.7)	6.9 (4.6 to 10.8)

No statistical analyses for this end point

Secondary: Phase 2: Progression-free Survival (PFS)

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End point title

Phase 2: Progression-free Survival (PFS) ^[14]

End point description

A PFS was defined as the time (in months) from the day of the first dose to the date of first objectively documented disease progression or death (any cause), whichever occurred first. Subjects who had died without a reported disease progression were considered to have progressed on the date of their death, subjects who did not progress or die were censored on the date of their last tumor assessment, subjects who had no on-study assessments and did not die were censored on the first dosing date, and subjects who started any subsequent anti-cancer therapy without a prior reported progression were censored at the last tumor assessment prior to initiation of the subsequent anti-cancer therapy. PFS was analysed as using Kaplan-Meier estimate. Efficacy population included all treated iCCA subjects with confirmed FGFR2 gene fusions or other FGFR2 rearrangements who had received at least 1 dose of TAS-120.

End point type

Secondary

End point timeframe

Up to approximately 37.5 months (through cut-off date 29-May-2021).

Notes
[14] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	103
Units: months
median (confidence interval 95%)	8.9 (6.7 to 11.0)

No statistical analyses for this end point

Secondary: Phase 1: Dose Expansion: Overall Survival (OS)

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End point title

Phase 1: Dose Expansion: Overall Survival (OS) ^[15]

End point description

An OS was defined as the time (in months) from the date of the first dose to the death date. In the absence of death confirmation or for subjects alive as of the OS cut-off date, survival time was censored at the date of last study follow-up, or the cut-off date, whichever was earlier. '9999' signifies that upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of subjects with events. '999' signifies that median was not estimable due to the smaller number of subjects with events. Efficacy population included all subjects who had received at least 1 dose of TAS-120. Data was planned to be collected and analysed on pooled population of subjects who received 16 mg of TAS-120 in the sub-cohorts 1 and 2.

End point type

Secondary

End point timeframe

Up to approximately 27.5 months (through cut-off date 30-Jun-2019).

Notes
[15] - 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 outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Pooled Sub-cohort
Number of subjects analysed	57	34	15	13	24	27	27
Units: months
median (confidence interval 95%)	11.4 (8.1 to 15.1)	11.8 (5.5 to 9999)	8.6 (2.1 to 9999)	5.8 (4.6 to 9999)	10.5 (6.7 to 9999)	7.2 (5.6 to 9999)	999 (12.2 to 9999)

No statistical analyses for this end point

Secondary: Phase 2: Overall Survival (OS)

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End point title

Phase 2: Overall Survival (OS) ^[16]

End point description

End point type

Secondary

End point timeframe

Up to approximately 37.5 months (through cut-off date 29-May-2021)

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	103
Units: months
median (confidence interval 95%)	20.0 (16.4 to 24.6)

No statistical analyses for this end point

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits

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End point title

Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits ^[17]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of subjects who chose each category. Patient-reported outcomes (PRO) Population that included all subjects who had received TAS-120 treatment and had EQ-5D-3L assessment at Baseline and at least one subsequent post-baseline assessment. Here, 'n' = number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[17] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in the Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: Count of subjects
Baseline - No Problem (n=90)	72
Baseline - Some Problem (n=90)	18
Baseline - Extreme Problem (n=90)	0
Cycle 2 - No Problem (n=81)	60
Cycle 2 - Some Problem (n=81)	20
Cycle 2 - Extreme Problem (n=81)	1
Cycle 4 - No Problem (n=78)	60
Cycle 4 - Some Problem (n=78)	18
Cycle 4 - Extreme Problem (n=78)	0
Cycle 7 - No Problem (n= 65)	51
Cycle 7 - Some Problem (n= 65)	14
Cycle 7 - Extreme Problem (n= 65)	0
Cycle 10 - No Problem (n= 58)	42
Cycle 10 - Some Problem (n= 58)	16
Cycle 10 - Extreme Problem (n= 58)	0
Cycle 13 - No Problem (n= 47)	32
Cycle 13 - Some Problem (n= 47)	15
Cycle 13 - Extreme Problem (n= 47)	0
Cycle 16 - No Problem (n= 35)	23
Cycle 16 - Some Problem (n= 35)	12
Cycle 16 - Extreme Problem (n= 35)	0
Cycle 19 - No Problem (n= 28)	16
Cycle 19 - Some Problem (n= 28)	12
Cycle 19 - Extreme Problem (n= 28)	0
Cycle 22 - No Problem (n= 21)	9
Cycle 22 - Some Problem (n= 21)	12
Cycle 22 - Extreme Problem (n= 21)	0
Cycle 25 - No Problem (n= 12)	9
Cycle 25 - Some Problem (n= 12)	2
Cycle 25 - Extreme Problem (n= 12)	1
Cycle 28 - No Problem (n= 8)	6
Cycle 28 - Some Problem (n= 8)	2
Cycle 28 - Extreme Problem (n= 8)	0
Cycle 31 - No Problem (n= 3)	3
Cycle 31 - Some Problem (n= 3)	0
Cycle 31 - Extreme Problem (n= 3)	0
Cycle 34 - No Problem (n= 3)	3
Cycle 34 - Some Problem (n= 3)	0
Cycle 34 - Extreme Problem (n= 3)	0
Cycle 37 - No Problem (n= 3)	2
Cycle 37 - Some Problem (n= 3)	1
Cycle 37 - Extreme Problem (n= 3)	0
Cycle 40 - No Problem (n= 1)	0
Cycle 40 - Some Problem (n= 1)	1
Cycle 40 - Extreme Problem (n= 1)	0
End of Treatment - No Problem (n= 44)	23
End of Treatment - Some Problem (n= 44)	20
End of Treatment - Extreme Problem (n= 44)	1

No statistical analyses for this end point

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits

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End point title

Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits ^[18]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of subjects who chose each category. Analysis was performed on PRO population. Here, 'n' = number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months])

Notes
[18] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: Count of subjects
Baseline - No Problem (n=90)	82
Baseline - Some Problem (n=90)	8
Baseline - Extreme Problem (n=90)	0
Cycle 2 - No Problem (n=81)	75
Cycle 2 - Some Problem (n=81)	6
Cycle 2 - Extreme Problem (n=81)	0
Cycle 4 - No Problem (n=78)	70
Cycle 4 - Some Problem (n=78)	7
Cycle 4 - Extreme Problem (n=78)	1
Cycle 7 - No Problem (n=65)	58
Cycle 7 - Some Problem (n=65)	6
Cycle 7 - Extreme Problem (n=65)	1
Cycle 10 - No Problem (n=58)	52
Cycle 10 - Some Problem (n=58)	6
Cycle 10 - Extreme Problem (n=58)	1
Cycle 13 - No Problem (n=47)	41
Cycle 13 - Some Problem (n=47)	6
Cycle 13 - Extreme Problem (n=47)	0
Cycle 16 - No Problem (n=35)	30
Cycle 16 - Some Problem (n=35)	4
Cycle 16 - Extreme Problem (n=35)	1
Cycle 19 - No Problem (n=28)	22
Cycle 19 - Some Problem (n=28)	6
Cycle 19 - Extreme Problem (n=28)	0
Cycle 22 - No Problem (n=21)	18
Cycle 22 - Some Problem (n=21)	3
Cycle 22 - Extreme Problem (n=21)	0
Cycle 25 - No Problem (n=12)	9
Cycle 25 - Some Problem (n=12)	3
Cycle 25 - Extreme Problem (n=12)	0
Cycle 28 - No Problem (n=8)	8
Cycle 28 - Some Problem (n=8)	0
Cycle 28 - Extreme Problem (n=8)	0
Cycle 31 - No Problem (n=3)	3
Cycle 31 - Some Problem (n=3)	0
Cycle 31 - Extreme Problem (n=3)	0
Cycle 34 - No Problem (n=3)	3
Cycle 34 - Some Problem (n=3)	0
Cycle 34 - Extreme Problem (n=3)	0
Cycle 37 - No Problem (n=3)	2
Cycle 37 - Some Problem (n=3)	1
Cycle 37 - Extreme Problem (n=3)	0
Cycle 40 - No Problem (n=1)	1
Cycle 40 - Some Problem (n=1)	0
Cycle 40 - Extreme Problem (n=1)	0
End of Treatment - No Problem (n= 43)	34
End of Treatment - Some Problem (n= 43)	8
End of Treatment - Extreme Problem (n= 43)	1

No statistical analyses for this end point

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits

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End point title

Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits ^[19]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of subjects who chose each category. Analysis was performed on PRO population. Here 'n' = number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: Count of subjects
Baseline - No Problem (n= 89)	63
Baseline - Some Problem (n= 89)	24
Baseline - Extreme Problem (n= 89)	2
Cycle 2 - No Problem (n= 81)	47
Cycle 2 - Some Problem (n= 81)	32
Cycle 2 - Extreme Problem (n= 81)	2
Cycle 4 - No Problem (n= 78)	50
Cycle 4 - Some Problem (n= 78)	27
Cycle 4 - Extreme Problem (n= 78)	1
Cycle 7 - No Problem (n= 65)	43
Cycle 7 - Some Problem (n= 65)	20
Cycle 7 - Extreme Problem (n= 65)	2
Cycle 10 - No Problem (n= 58)	34
Cycle 10 - Some Problem (n= 58)	23
Cycle 10 - Extreme Problem (n= 58)	1
Cycle 13 - No Problem (n= 47)	28
Cycle 13 - Some Problem (n= 47)	19
Cycle 13 - Extreme Problem (n= 47)	0
Cycle 16 - No Problem (n= 35)	20
Cycle 16 - Some Problem (n= 35)	14
Cycle 16 - Extreme Problem (n= 35)	1
Cycle 19 - No Problem (n= 28)	15
Cycle 19 - Some Problem (n= 28)	12
Cycle 19 - Extreme Problem (n= 28)	1
Cycle 22 - No Problem (n= 21)	7
Cycle 22 - Some Problem (n= 21)	14
Cycle 22 - Extreme Problem (n= 21)	0
Cycle 25 - No Problem (n= 12)	4
Cycle 25 - Some Problem (n= 12)	7
Cycle 25 - Extreme Problem (n= 12)	1
Cycle 28 - No Problem (n= 8)	3
Cycle 28 - Some Problem (n= 8)	5
Cycle 28 - Extreme Problem (n= 8)	0
Cycle 31 - No Problem (n= 3)	1
Cycle 31 - Some Problem (n= 3)	2
Cycle 31 - Extreme Problem (n= 3)	0
Cycle 34 - No Problem (n= 3)	2
Cycle 34 - Some Problem (n= 3)	1
Cycle 34 - Extreme Problem (n= 3)	0
Cycle 37 - No Problem (n= 3)	0
Cycle 37 - Some Problem (n= 3)	3
Cycle 37 - Extreme Problem (n= 3)	0
Cycle 40 - No Problem (n= 1)	0
Cycle 40 - Some Problem (n= 1)	1
Cycle 40 - Extreme Problem (n= 1)	0
End of Treatment - No Problem (n= 44)	16
End of Treatment - Some Problem (n= 44)	25
End of Treatment - Extreme Problem (n= 44)	3

No statistical analyses for this end point

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits

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End point title

Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits ^[20]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of subjects who chose each category. Analysis was performed on PRO population. Here, 'n' = number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: Count of subjects
Baseline - No Problem (n=90)	42
Baseline - Some Problem (n=90)	47
Baseline - Extreme Problem (n=90)	1
Cycle 2 - No Problem (n=81)	45
Cycle 2 - Some Problem (n=81)	35
Cycle 2 - Extreme Problem (n=81)	1
Cycle 4 - No Problem (n=78)	40
Cycle 4 - Some Problem (n=78)	36
Cycle 4 - Extreme Problem (n=78)	2
Cycle 7 - No Problem (n=66)	36
Cycle 7 - Some Problem (n=66)	29
Cycle 7 - Extreme Problem (n=66)	1
Cycle 10 - No Problem (n=58)	30
Cycle 10 - Some Problem (n=58)	26
Cycle 10 - Extreme Problem (n=58)	2
Cycle 13 - No Problem (n=47)	23
Cycle 13 - Some Problem (n=47)	22
Cycle 13 - Extreme Problem (n=47)	2
Cycle 16 - No Problem (n=35)	13
Cycle 16 - Some Problem (n=35)	19
Cycle 16 - Extreme Problem (n=35)	3
Cycle 19 - No Problem (n=28)	13
Cycle 19 - Some Problem (n=28)	15
Cycle 19 - Extreme Problem (n=28)	0
Cycle 22 - No Problem (n=21)	6
Cycle 22 - Some Problem (n=21)	14
Cycle 22 - Extreme Problem (n=21)	1
Cycle 25 - No Problem (n=12)	3
Cycle 25 - Some Problem (n=12)	9
Cycle 25 - Extreme Problem (n=12)	0
Cycle 28 - No Problem (n=8)	2
Cycle 28 - Some Problem (n=8)	5
Cycle 28 - Extreme Problem (n=8)	1
Cycle 31 - No Problem (n=3)	2
Cycle 31 - Some Problem (n=3)	1
Cycle 31 - Extreme Problem (n=3)	0
Cycle 34 - No Problem (n=3)	3
Cycle 34 - Some Problem (n=3)	0
Cycle 34 - Extreme Problem (n=3)	0
Cycle 37 - No Problem (n=3)	2
Cycle 37 - Some Problem (n=3)	1
Cycle 37 - Extreme Problem (n=3)	0
Cycle 40 - No Problem (n=1)	0
Cycle 40 - Some Problem (n=1)	1
Cycle 40 - Extreme Problem (n=1)	0
End of Treatment - No Problem (n=44)	12
End of Treatment - Some Problem (n=44)	27
End of Treatment - Extreme Problem (n=44)	5

No statistical analyses for this end point

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits

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End point title

Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits ^[21]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension was rated on 3 levels of function: no problem, some problem and extreme problem. In this outcome measure, data were reported categorically as the number of subjects who chose each category. Analysis was performed on PRO population. Here, 'n' = number of subject s with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: Count of subjects
Baseline - No Problem (n= 89)	64
Baseline - Some Problem (n= 89)	25
Baseline - Extreme Problem (n= 89)	0
Cycle 2 - No Problem (n= 81)	66
Cycle 2 - Some Problem (n= 81)	15
Cycle 2 - Extreme Problem (n= 81)	0
Cycle 4 - No Problem (n= 78)	63
Cycle 4 - Some Problem (n= 78)	15
Cycle 4 - Extreme Problem (n= 78)	0
Cycle 7 - No Problem (n= 65)	48
Cycle 7 - Some Problem (n= 65)	15
Cycle 7 - Extreme Problem (n= 65)	2
Cycle 10 - No Problem (n= 58)	44
Cycle 10 - Some Problem (n= 58)	12
Cycle 10 - Extreme Problem (n= 58)	2
Cycle 13 - No Problem (n= 47)	36
Cycle 13 - Some Problem (n= 47)	11
Cycle 13 - Extreme Problem (n= 47)	0
Cycle 16 - No Problem (n= 35)	26
Cycle 16 - Some Problem (n= 35)	8
Cycle 16 - Extreme Problem (n= 35)	1
Cycle 19 - No Problem (n= 23)	21
Cycle 19 - Some Problem (n= 23)	6
Cycle 19 - Extreme Problem (n= 23)	1
Cycle 22 - No Problem (n= 21)	13
Cycle 22 - Some Problem (n= 21)	8
Cycle 22 - Extreme Problem (n= 21)	0
Cycle 25 - No Problem (n= 12)	8
Cycle 25 - Some Problem (n= 12)	4
Cycle 25 - Extreme Problem (n= 12)	0
Cycle 28 - No Problem (n= 8)	5
Cycle 28 - Some Problem (n= 8)	3
Cycle 28 - Extreme Problem (n= 8)	0
Cycle 31 - No Problem (n= 3)	2
Cycle 31 - Some Problem (n= 3)	1
Cycle 31 - Extreme Problem (n= 3)	0
Cycle 34 - No Problem (n= 3)	2
Cycle 34 - Some Problem (n= 3)	1
Cycle 34 - Extreme Problem (n= 3)	0
Cycle 37 - No Problem (n= 3)	1
Cycle 37 - Some Problem (n= 3)	2
Cycle 37 - Extreme Problem (n= 3)	0
Cycle 40 - No Problem (n= 1)	0
Cycle 40 - Some Problem (n= 1)	1
Cycle 40 - Extreme Problem (n= 1)	0
End of Treatment - No Problem (n= 44)	22
End of Treatment - Some Problem (n= 44)	19
End of Treatment - Extreme Problem (n= 44)	3

No statistical analyses for this end point

Secondary: Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits

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End point title

Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits ^[22]

End point description

EQ-5D-3L was a self-administered standardized questionnaire to assess health outcome. It comprised 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A vertical VAS allows the subjects to indicate their health state that day, and ranged from 0 (worst imaginable) to 100 (best imaginable), with higher scores indicating better health state. Analysis was performed on PRO population. Here, 'n' = number of subjects with available data for each specified category. '9999’ signifies that the SD was not calculable for 1 subject.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: score on a scale
arithmetic mean (standard deviation)
Baseline (n= 88)	71.72 ( 20.307 )
Change at Cycle 2 (n= 77)	-0.73 ( 19.409 )
Change at Cycle 4 (n= 74)	-1.04 ( 23.984 )
Change at Cycle 7 (n= 62)	-1.82 ( 29.984 )
Change at Cycle 10 (n= 54)	0.40 ( 30.428 )
Change at Cycle 13 (n= 45)	4.76 ( 26.585 )
Change at Cycle 16 (n= 33)	-1.71 ( 34.417 )
Change at Cycle 19 (n= 27)	1.76 ( 25.155 )
Change at Cycle 22 (n= 20)	1.85 ( 31.707 )
Change at Cycle 25 (n= 11)	-0.82 ( 45.828 )
Change at Cycle 28 (n= 8)	-1.85 ( 40.912 )
Change at Cycle 31 (n= 3)	18.17 ( 17.280 )
Change at Cycle 34 (n= 3)	19.00 ( 19.313 )
Change at Cycle 37 (n= 3)	15.17 ( 21.624 )
Change at Cycle 40 (n= 1)	15.00 ( 9999 )
End of Treatment (n= 44)	-8.89 ( 26.272 )

No statistical analyses for this end point

Secondary: Phase 2: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints

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End point title

Phase 2: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints ^[23]

End point description

The EORTC QLQ-C30 is a 30-item cancer-specific tool used to evaluate chemotherapy effects and subject-reported outcomes. It covers global health status/quality of life (GHS/QOL), five functional scales (physical, role, cognitive, emotional, social), three symptom scales (fatigue, pain, nausea/vomiting), and six single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most items use a 4-point scale (1=Not at All to 4=Very Much), while Items 29–30 form the GHS scale, scored on a 7-point scale (1=Very Poor to 7=Excellent). GHS total score = ([{Q29+Q30}/2]−1)/6×100. Scores range from 0 (worst) to 100 (best); higher scores indicate better quality of life. ‘9999’ signifies that upper limit of 95% confidence interval (CI) was not estimable due to the smaller number of subjects with events. Analysis was performed on PRO population. Here, 'n' = number of subjects with available data for each specified category.

End point type

Secondary

End point timeframe

Baseline, Cycle 2, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40 and end of treatment (i.e., Cycle 43 [30 months]).

Notes
[23] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	92
Units: score on scale
arithmetic mean (standard deviation)
Baseline (n= 91)	70.1 ( 19.41 )
Change at Cycle 2 (n= 83)	-1.0 ( 22.02 )
Change at Cycle 4 (n=79)	0.4 ( 20.62 )
Change at Cycle 7 (n= 65)	-0.5 ( 21.64 )
Change at Cycle 10 (n= 58)	1.9 ( 22.84 )
Change at Cycle 13 (n= 48)	0.9 ( 21.49 )
Change at Cycle 16 (n= 27)	2.5 ( 18.61 )
Change at Cycle 19 (n= 15)	-1.7 ( 17.31 )
Change at Cycle 22 (n= 11)	-8.3 ( 22.05 )
Change at Cycle 25 (n= 7)	-4.8 ( 21.44 )
Change at Cycle 28 (n= 4)	-6.3 ( 12.50 )
Change at Cycle 31 (n= 1)	41.7 ( 9999 )
Change at Cycle 34 (n= 1)	41.7 ( 9999 )
End of Treatment (n=30)	-7.5 ( 23.30 )

No statistical analyses for this end point

Secondary: Phase 1: Dose Expansion: Number of Subjects with Any Adverse Events (AEs) and Any Serious AEs (SAEs)

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End point title

Phase 1: Dose Expansion: Number of Subjects with Any Adverse Events (AEs) and Any Serious AEs (SAEs) ^[24]

End point description

An AE was defined as any untoward medical condition that occurred in a subject from the time the ICF was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event. Safety Population subjects included all subjects who had received at least 1 dose of TAS-120.

End point type

Secondary

End point timeframe

From the first dose up to approximately 50.5 months (through cut-off date 29-May-2021).

Notes
[24] - 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 outcome measure was planned to be reported for only Cohort 1 as pre-specified in Protocol and SAP.

End point values	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Sub-cohort 1	Phase 1: Dose Expansion: Sub-cohort 2
Number of subjects analysed	57	34	15	13	24	27	19	8
Units: Count of subjects
AEs	57	34	15	13	23	26	18	5
SAEs	27	13	10	9	13	14	0	0

No statistical analyses for this end point

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

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End point title

Phase 2: Number of Subjects with Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) ^[25]

End point description

An AE was defined as any untoward medical condition that occurs in a subject from the time the ICF was signed and does not necessarily had a causal relationship with the use of the product. An SAE was an AE that falls into one or more of the following categories: a. resulted in death, b. was life threatening, c. required inpatient hospitalization or prolongation of existing hospitalization, d. resulted in persistent or significant disability or incapacity, e. was a congenital anomaly/birth defect, f. other important medical event. Safety Population included all subjects who had received at least 1 dose of TAS-120.

End point type

Secondary

End point timeframe

From the first dose up to approximately 37.5 months (through cut-off date 29-May-2021).

Notes
[25] - 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 outcome measure was planned to be reported for only Cohort 2 as pre-specified in Protocol and SAP.

End point values	Phase 2
Number of subjects analysed	103
Units: Count of subjects
AEs	103
SAEs	42

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From the first dose administration up to approximately up to 59.5 months for Phase 1 Dose escalation; up to 50.5 months for Phase 1 Dose expansion Cohorts and up to 37.5 months for Phase 2

Adverse event reporting additional description

Safety Population included all subjects who had received at least 1 dose of TAS-120. MedDRA version 17.0 for Phase 1 and MedDRA version 22.0 for Phase 2. Safety analysis were done based on data cut-off dates: 12 July 2019 for Phase 1 Dose Escalation, 29-May-2021 for Phase 1 Dose Expansion and Phase 2.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

17.0, 22.0

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 8 mg

Reporting group description

Subjects with or without fibroblast growth factor [FGF]/fibroblast growth factor receptor [FGFR] gene abnormalities received TAS-120 8 milligrams (mg) orally every other day (QOD; Monday, Wednesday and Friday of each week) in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 16 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 24 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 36 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 56 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 80 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 120 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 160 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QOD Dosing: 200 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 4 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 8 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 16 mg

Reporting group description

Subjects with or without FGF/FGFR gene abnormalities received a dose between 16 mg orally QD in a 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death.

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 20 mg

Reporting group description

Reporting group title

Phase 1: Dose Escalation: QD Dosing: 24 mg

Reporting group description

Reporting group title

Phase 1: Dose Expansion Cohort 1

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 2

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 3

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 4

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Cohort 5

Reporting group description

Subjects with tumor types harboring FGFR gene fusions or activating mutations received TAS-120 20 mg tablets orally QD in each of 21- day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 42.5 months).

Reporting group title

Phase 1: Dose Expansion: Cohort 6

Reporting group description

Subjects who were not included in Cohorts 1 to 5 received TAS-120 20 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 11 months).

Reporting group title

Phase 1: Dose Expansion: Sub-cohort 2

Reporting group description

Reporting group title

Phase 1: Dose Expansion: Sub-cohort 1

Reporting group description

Subjects with iCCA who were enrolled prior to the confirmation of the RP2D received TAS-120 16 mg tablets orally QD in each of 21-day treatment cycle until disease progression, unacceptable toxicity, withdrawal of consent or death (maximum exposure: 28 months).

Reporting group title

Phase 2

Reporting group description

Phase 1: Dose Escalation: QOD Dosing: 8 mg

Phase 1: Dose Escalation: QOD Dosing: 16 mg

Phase 1: Dose Escalation: QOD Dosing: 24 mg

Phase 1: Dose Escalation: QOD Dosing: 36 mg

Phase 1: Dose Escalation: QOD Dosing: 56 mg

Phase 1: Dose Escalation: QOD Dosing: 80 mg

Phase 1: Dose Escalation: QOD Dosing: 120 mg

Phase 1: Dose Escalation: QOD Dosing: 160 mg

Phase 1: Dose Escalation: QOD Dosing: 200 mg

Phase 1: Dose Escalation: QD Dosing: 4 mg

Phase 1: Dose Escalation: QD Dosing: 8 mg

Phase 1: Dose Escalation: QD Dosing: 16 mg

Phase 1: Dose Escalation: QD Dosing: 20 mg

Phase 1: Dose Escalation: QD Dosing: 24 mg

Phase 1: Dose Expansion Cohort 1

Phase 1: Dose Expansion: Cohort 2

Phase 1: Dose Expansion: Cohort 3

Phase 1: Dose Expansion: Cohort 4

Phase 1: Dose Expansion: Cohort 5

Phase 1: Dose Expansion: Cohort 6

Phase 1: Dose Expansion: Sub-cohort 2

Phase 1: Dose Expansion: Sub-cohort 1

Phase 2

Total subjects affected by serious adverse events

subjects affected / exposed

1 / 6 (16.67%)

0 / 3 (0.00%)

1 / 3 (33.33%)

2 / 5 (40.00%)

4 / 4 (100.00%)

7 / 8 (87.50%)

4 / 7 (57.14%)

0 / 4 (0.00%)

1 / 5 (20.00%)

9 / 14 (64.29%)

3 / 7 (42.86%)

6 / 14 (42.86%)

27 / 57 (47.37%)

13 / 34 (38.24%)

10 / 15 (66.67%)

9 / 13 (69.23%)

13 / 24 (54.17%)

14 / 27 (51.85%)

0 / 8 (0.00%)

0 / 19 (0.00%)

42 / 103 (40.78%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Colon cancer metastatic

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Malignant ascites

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Malignant neoplasm progression

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Malignant pleural effusion

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metastases to central nervous system

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Tumour associated fever

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tumour pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep vein thrombosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Jugular vein thrombosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Death

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Disease progression

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

2 / 7 (28.57%)

1 / 14 (7.14%)

2 / 57 (3.51%)

0 / 34 (0.00%)

3 / 15 (20.00%)

2 / 13 (15.38%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

5 / 103 (4.85%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 1

0 / 2

0 / 0

0 / 3

0 / 2

0 / 0

0 / 2

0 / 0

0 / 6

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

Fatigue

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gait disturbance

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

4 / 103 (3.88%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 4

deaths causally related to treatment / all

0 / 0

Suprapubic pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Aspiration

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Epistaxis

subjects affected / exposed

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

1 / 5 (20.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary thrombosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory distress

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Respiratory failure

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Disorientation

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mental status changes

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gamma-glutamyltransferase increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nuclear magnetic resonance imaging brain abnormal

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Troponin T increased

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Femur fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Humerus fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Muscle strain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Overdose

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Post procedural fever

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Rib fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Spinal compression fracture

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subdural haematoma

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Acute myocardial infarction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial fibrillation

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ventricular tachycardia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Altered state of consciousness

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aphasia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cerebral ischaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cognitive disorder

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dizziness

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dysarthria

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Extrapyramidal disorder

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Focal dyscognitive seizures

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Guillain-Barre syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

2 / 34 (5.88%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Hemiparesis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

2 / 34 (5.88%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Intracranial mass

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Migraine

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Nervous system disorder

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neurological symptom

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paraesthesia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Presyncope

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal cord compression

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Subarachnoid haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 5 (20.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Hepatic encephalopathy

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 2

0 / 0

0 / 2

0 / 0

2 / 3

deaths causally related to treatment / all

0 / 0

Eye disorders

Cataract

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Ocular ischaemic syndrome

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Papilloedema

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Retinal detachment

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

2 / 8 (25.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

3 / 57 (5.26%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 1

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

4 / 103 (3.88%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 4

deaths causally related to treatment / all

0 / 0

0 / 1

Colitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Colonic pseudo-obstruction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

1 / 7 (14.29%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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 obstruction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

deaths causally related to treatment / all

0 / 0

Gastric haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Haematemesis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Haematochezia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ileus

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Impaired gastric emptying

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Inguinal hernia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

2 / 24 (8.33%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Melaena

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

1 / 7 (14.29%)

1 / 14 (7.14%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Obstruction gastric

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oesophageal ulcer

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oesophageal varices haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Oesophagitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 3

deaths causally related to treatment / all

0 / 0

Oesophagitis ulcerative

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pancreatitis acute

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Small intestinal haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Stomatitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Umbilical hernia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

3 / 103 (2.91%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 4

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

1 / 7 (14.29%)

1 / 14 (7.14%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Bile duct obstruction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

3 / 103 (2.91%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Bile duct stenosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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 / 6 (0.00%)

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Cholangitis acute

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholecystitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gallbladder obstruction

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatic failure

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

Jaundice

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Portal vein thrombosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Hydronephrosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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 incontinence

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary retention

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bone pain

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Haemarthrosis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Muscular weakness

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Myalgia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Appendicitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Biliary sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Biliary tract infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bronchitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Corona virus infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cystitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastroenteritis viral

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

1 / 14 (7.14%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (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

Lung infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Paronychia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritonitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Peritonitis bacterial

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pharyngitis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

1 / 7 (14.29%)

0 / 14 (0.00%)

0 / 57 (0.00%)

1 / 34 (2.94%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

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 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

1 / 7 (14.29%)

0 / 14 (0.00%)

3 / 57 (5.26%)

1 / 34 (2.94%)

0 / 15 (0.00%)

1 / 13 (7.69%)

0 / 24 (0.00%)

3 / 27 (11.11%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Splenic abscess

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 4

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

1 / 15 (6.67%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wound infection

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

1 / 24 (4.17%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

Dehydration

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

1 / 14 (7.14%)

1 / 7 (14.29%)

0 / 14 (0.00%)

2 / 57 (3.51%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

1 / 27 (3.70%)

0 / 8 (0.00%)

0 / 19 (0.00%)

2 / 103 (1.94%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

Failure to thrive

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

0 / 103 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypercalcaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyperkalaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

1 / 57 (1.75%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 4 (0.00%)

0 / 5 (0.00%)

0 / 14 (0.00%)

0 / 7 (0.00%)

0 / 14 (0.00%)

0 / 57 (0.00%)

0 / 34 (0.00%)

0 / 15 (0.00%)

0 / 13 (0.00%)

0 / 24 (0.00%)

0 / 27 (0.00%)

0 / 8 (0.00%)

0 / 19 (0.00%)

1 / 103 (0.97%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Phase 1: Dose Escalation: QOD Dosing: 8 mg	Phase 1: Dose Escalation: QOD Dosing: 16 mg	Phase 1: Dose Escalation: QOD Dosing: 24 mg	Phase 1: Dose Escalation: QOD Dosing: 36 mg	Phase 1: Dose Escalation: QOD Dosing: 56 mg	Phase 1: Dose Escalation: QOD Dosing: 80 mg	Phase 1: Dose Escalation: QOD Dosing: 120 mg	Phase 1: Dose Escalation: QOD Dosing: 160 mg	Phase 1: Dose Escalation: QOD Dosing: 200 mg	Phase 1: Dose Escalation: QD Dosing: 4 mg	Phase 1: Dose Escalation: QD Dosing: 8 mg	Phase 1: Dose Escalation: QD Dosing: 16 mg	Phase 1: Dose Escalation: QD Dosing: 20 mg	Phase 1: Dose Escalation: QD Dosing: 24 mg	Phase 1: Dose Expansion Cohort 1	Phase 1: Dose Expansion: Cohort 2	Phase 1: Dose Expansion: Cohort 3	Phase 1: Dose Expansion: Cohort 4	Phase 1: Dose Expansion: Cohort 5	Phase 1: Dose Expansion: Cohort 6	Phase 1: Dose Expansion: Sub-cohort 2	Phase 1: Dose Expansion: Sub-cohort 1	Phase 2
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	5 / 5 (100.00%)	4 / 4 (100.00%)	8 / 8 (100.00%)	7 / 7 (100.00%)	4 / 4 (100.00%)	5 / 5 (100.00%)	14 / 14 (100.00%)	7 / 7 (100.00%)	14 / 14 (100.00%)	57 / 57 (100.00%)	34 / 34 (100.00%)	15 / 15 (100.00%)	13 / 13 (100.00%)	23 / 24 (95.83%)	26 / 27 (96.30%)	8 / 8 (100.00%)	19 / 19 (100.00%)	103 / 103 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1
Skin papilloma
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	2 / 19 (10.53%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	2
Tumour haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Tumour pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	2 / 13 (15.38%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	5 / 103 (4.85%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	3	0	1	0	0	5
Infected neoplasm
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Vascular disorders
Hot flush
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Hypertension
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2	0	0	1	0	0	19
Phlebitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	1	0	0	0	0	0	0
Venous thrombosis limb
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hypotension
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	2 / 7 (28.57%)	1 / 14 (7.14%)	4 / 57 (7.02%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 27 (7.41%)	0 / 8 (0.00%)	4 / 19 (21.05%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	4	1	7	1	0	1	1	3	0	6	6
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 6 (16.67%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 5 (0.00%)	4 / 14 (28.57%)	1 / 7 (14.29%)	2 / 14 (14.29%)	7 / 57 (12.28%)	7 / 34 (20.59%)	2 / 15 (13.33%)	0 / 13 (0.00%)	4 / 24 (16.67%)	6 / 27 (22.22%)	1 / 8 (12.50%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	1	2	0	2	1	1	0	2	2	1	0	4	1	2	10	15	2	0	4	9	0	3	7
Chills
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 27 (11.11%)	0 / 8 (0.00%)	0 / 19 (0.00%)	4 / 103 (3.88%)
occurrences all number	3	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	6	0	0	5
Fatigue
subjects affected / exposed	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 14 (14.29%)	1 / 7 (14.29%)	2 / 14 (14.29%)	12 / 57 (21.05%)	9 / 34 (26.47%)	4 / 15 (26.67%)	6 / 13 (46.15%)	8 / 24 (33.33%)	9 / 27 (33.33%)	2 / 8 (25.00%)	4 / 19 (21.05%)	36 / 103 (34.95%)
occurrences all number	1	1	1	0	0	1	2	6	1	0	3	2	1	3	14	12	5	6	18	15	2	5	65
Influenza like illness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
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
Mucosal dryness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	4 / 103 (3.88%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	2	0	0	4
Oedema peripheral
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	8 / 57 (14.04%)	0 / 34 (0.00%)	3 / 15 (20.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	15 / 103 (14.56%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	1	8	0	5	0	3	2	0	3	17
Pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0	1	0	1	3
Peripheral swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	2
Pyrexia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 7 (14.29%)	1 / 14 (7.14%)	4 / 57 (7.02%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	2 / 24 (8.33%)	2 / 27 (7.41%)	0 / 8 (0.00%)	3 / 19 (15.79%)	11 / 103 (10.68%)
occurrences all number	0	0	0	0	1	1	0	1	1	1	0	1	1	1	5	0	0	2	2	2	0	3	15
Xerosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	1	0	1	0	1	0	0	0	0	0	0	0	0	0
Device failure
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Disease progression
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	2 / 7 (28.57%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	2	1	0	0	0	0	0	0	0	0	0
Face oedema
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Gait disturbance
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Chest discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Chest pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Reproductive system and breast disorders
Benign prostatic hyperplasia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Pelvic pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	1	1	0	0	0	1	0	0	0	1	0	0	4	0	1	0	0	0	0	0	1
Vulvovaginal dryness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	1	0
Breast ulceration
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Ovarian vein thrombosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Vaginal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Cough
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	2 / 14 (14.29%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 27 (3.70%)	0 / 8 (0.00%)	2 / 19 (10.53%)	4 / 103 (3.88%)
occurrences all number	0	1	0	0	1	0	0	0	0	1	0	2	0	2	3	0	0	0	2	1	0	2	4
Dysphonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
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
Dyspnoea
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	3 / 14 (21.43%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	1 / 34 (2.94%)	0 / 15 (0.00%)	2 / 13 (15.38%)	5 / 24 (20.83%)	4 / 27 (14.81%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	3	0	0	4	1	0	3	5	6	0	1	6
Dyspnoea exertional
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	1	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	1 / 14 (7.14%)	3 / 57 (5.26%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	4 / 19 (21.05%)	7 / 103 (6.80%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	1	2	0	1	3	1	0	1	0	0	0	4	8
Hiccups
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2	1	0	0	0	0	0	3
Hypoxia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	6
Oropharyngeal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 57 (1.75%)	3 / 34 (8.82%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	10 / 103 (9.71%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	3	0	0	1	0	0	2	10
Pleural effusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	1 / 19 (5.26%)	0 / 103 (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
Pneumothorax
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
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	2
Pulmonary embolism
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1	0	0	0	0	0	0
Rhinitis allergic
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Throat irritation
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (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
Upper-airway cough syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
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
Dry throat
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Haemoptysis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hypoventilation
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Nasal dryness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0
Pleurisy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
Rhinalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Oropharyngeal dysplasia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	0 / 15 (0.00%)	2 / 13 (15.38%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0	1	0	0	2
Confusional state
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	2 / 8 (25.00%)	1 / 19 (5.26%)	5 / 103 (4.85%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1	2	0	0	0	0	2	1	5
Insomnia
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	5 / 57 (8.77%)	0 / 34 (0.00%)	0 / 15 (0.00%)	2 / 13 (15.38%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	3 / 19 (15.79%)	8 / 103 (7.77%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0	0	0	1	6	0	0	2	3	0	0	4	9
Onychophagia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (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
Agitation
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Delirium
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Depression
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hallucination
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Libido decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
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	3
Aspartate aminotransferase increased
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)	1 / 4 (25.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	3 / 7 (42.86%)	5 / 14 (35.71%)	16 / 57 (28.07%)	8 / 34 (23.53%)	2 / 15 (13.33%)	5 / 13 (38.46%)	6 / 24 (25.00%)	9 / 27 (33.33%)	0 / 8 (0.00%)	7 / 19 (36.84%)	26 / 103 (25.24%)
occurrences all number	1	0	0	0	0	1	0	0	3	1	1	2	4	11	33	14	3	11	18	13	0	11	60
Bilirubin conjugated increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2	0	0	0
Blood albumin decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	8 / 57 (14.04%)	3 / 34 (8.82%)	2 / 15 (13.33%)	2 / 13 (15.38%)	2 / 24 (8.33%)	3 / 27 (11.11%)	0 / 8 (0.00%)	4 / 19 (21.05%)	13 / 103 (12.62%)
occurrences all number	0	0	0	0	0	1	0	0	2	2	1	0	0	1	19	3	2	2	4	6	0	7	25
Blood bilirubin increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	2 / 14 (14.29%)	9 / 57 (15.79%)	2 / 34 (5.88%)	1 / 15 (6.67%)	1 / 13 (7.69%)	2 / 24 (8.33%)	1 / 27 (3.70%)	1 / 8 (12.50%)	1 / 19 (5.26%)	7 / 103 (6.80%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	6	19	2	2	2	5	4	2	2	20
Blood calcium increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	3	0	2	1
Blood creatine phosphokinase increased
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	10 / 103 (9.71%)
occurrences all number	1	0	0	0	0	0	0	5	0	0	0	1	0	0	4	0	0	0	1	1	0	3	12
Blood creatinine increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	9 / 57 (15.79%)	2 / 34 (5.88%)	3 / 15 (20.00%)	1 / 13 (7.69%)	3 / 24 (12.50%)	3 / 27 (11.11%)	0 / 8 (0.00%)	5 / 19 (26.32%)	15 / 103 (14.56%)
occurrences all number	0	0	1	0	0	0	0	6	0	0	0	1	0	1	14	4	8	3	3	4	0	8	30
Blood phosphorus increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	9 / 103 (8.74%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	10	4	0	0	0	0	0	0	30
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 57 (1.75%)	3 / 34 (8.82%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	1	0	1	0	4	3	0	0	1	0	0	0	4
International normalised ratio increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	2
Lymphocyte count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	1	0	0	0	9
Neutrophil count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	2	6
Platelet count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	3 / 57 (5.26%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	2 / 19 (10.53%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	4	2	0	0	0	2	0	7	6
Troponin T increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	7 / 103 (6.80%)
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	8
Urine analysis abnormal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	2 / 15 (13.33%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	1
Weight decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	10 / 57 (17.54%)	2 / 34 (5.88%)	2 / 15 (13.33%)	1 / 13 (7.69%)	4 / 24 (16.67%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	19 / 103 (18.45%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	1	0	1	15	2	3	2	5	1	0	5	29
Weight increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	3 / 34 (8.82%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	3	0	0	0	4
White blood cell count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	2	6
Lipase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Platelet count increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Amylase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood creatine phosphokinase decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Blood thyroid stimulating hormone increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Gastric pH decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram ST segment abnormal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Accidental overdose
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Burn oesophageal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Fall
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0
Muscle rupture
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Post procedural haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Post procedural oedema
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Stoma site pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Wound decomposition
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Wound haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	0 / 103 (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	3	0
Tachycardia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
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	2
Sinus tachycardia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0	0	1
Balance disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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	0	0
Dizziness
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	1 / 14 (7.14%)	7 / 57 (12.28%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	5 / 19 (26.32%)	10 / 103 (9.71%)
occurrences all number	1	0	0	0	0	1	0	1	0	0	1	2	0	1	9	2	0	1	0	1	0	7	11
Dysgeusia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	3 / 14 (21.43%)	7 / 57 (12.28%)	2 / 34 (5.88%)	2 / 15 (13.33%)	0 / 13 (0.00%)	3 / 24 (12.50%)	3 / 27 (11.11%)	0 / 8 (0.00%)	3 / 19 (15.79%)	21 / 103 (20.39%)
occurrences all number	0	0	0	0	0	0	0	2	1	0	0	0	0	3	8	2	4	0	3	4	0	3	27
Headache
subjects affected / exposed	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	5 / 57 (8.77%)	6 / 34 (17.65%)	2 / 15 (13.33%)	1 / 13 (7.69%)	3 / 24 (12.50%)	0 / 27 (0.00%)	0 / 8 (0.00%)	4 / 19 (21.05%)	8 / 103 (7.77%)
occurrences all number	2	0	0	0	0	1	0	6	1	0	0	1	0	0	12	6	2	1	4	0	0	6	13
Hemiparesis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	4 / 34 (11.76%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6	0	0	0	0	0	0	0
Hypoaesthesia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	4 / 34 (11.76%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	7 / 103 (6.80%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	4	0	0	0	0	0	1	9
Memory impairment
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	1
Neuropathy peripheral
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	1 / 14 (7.14%)	3 / 57 (5.26%)	0 / 34 (0.00%)	1 / 15 (6.67%)	2 / 13 (15.38%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0	2	0	1	3	0	1	2	1	0	0	0	7
Paraesthesia
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	2 / 14 (14.29%)	2 / 57 (3.51%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	1 / 8 (12.50%)	0 / 19 (0.00%)	5 / 103 (4.85%)
occurrences all number	1	0	0	0	0	0	0	0	2	0	0	0	0	2	3	1	0	0	0	1	1	0	6
Peripheral sensory neuropathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	1 / 34 (2.94%)	1 / 15 (6.67%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	10 / 103 (9.71%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	5	1	1	0	1	0	0	0	15
Seizure
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	2	0	0	1	2	0	0	4
Tremor
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	3 / 103 (2.91%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	3
Cognitive disorder
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Aphasia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ataxia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Disturbance in attention
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Dysarthria
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Encephalopathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Migraine with aura
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Partial seizures
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Nervous system disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Peroneal nerve palsy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Migraine
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
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	3
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 5 (20.00%)	2 / 4 (50.00%)	4 / 8 (50.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	3 / 7 (42.86%)	3 / 14 (21.43%)	10 / 57 (17.54%)	4 / 34 (11.76%)	2 / 15 (13.33%)	3 / 13 (23.08%)	4 / 24 (16.67%)	5 / 27 (18.52%)	1 / 8 (12.50%)	2 / 19 (10.53%)	17 / 103 (16.50%)
occurrences all number	3	0	0	2	1	1	3	8	1	1	0	2	3	7	14	4	2	9	10	7	4	2	36
Iron deficiency anaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Lymphopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	4	0	0	0	2	5
Neutropenia
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	1	1	0	1	6
Thrombocytopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 7 (14.29%)	1 / 14 (7.14%)	3 / 57 (5.26%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	12 / 103 (11.65%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	1	2	1	3	2	0	0	2	2	0	1	27
Increased tendency to bruise
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Lymph node pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Lymphadenopathy mediastinal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	1	0	1
Tinnitus
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	0	2	0	1
Vertigo
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0	1	0	0	4
Cerumen impaction
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Eye disorders
Cataract
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	8 / 57 (14.04%)	0 / 34 (0.00%)	0 / 15 (0.00%)	3 / 13 (23.08%)	2 / 24 (8.33%)	2 / 27 (7.41%)	1 / 8 (12.50%)	1 / 19 (5.26%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	16	0	0	3	3	3	1	8	6
Cataract nuclear
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	2 / 15 (13.33%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	1	0	1	0	1	0
Cataract subcapsular
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Chorioretinopathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	2
Dry eye
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	1 / 5 (20.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	2 / 14 (14.29%)	7 / 57 (12.28%)	0 / 34 (0.00%)	1 / 15 (6.67%)	2 / 13 (15.38%)	3 / 24 (12.50%)	5 / 27 (18.52%)	0 / 8 (0.00%)	2 / 19 (10.53%)	23 / 103 (22.33%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	1	2	0	2	7	0	1	2	4	5	0	2	28
Eye irritation
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Eye pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	5
Growth of eyelashes
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	3	0	0	1	0	0	0	1	1
Keratitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	3	0	0	1	0	3	0	0	1
Lacrimation decreased
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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	0	0
Optic nerve cupping
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Photopsia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Visual acuity reduced
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vitreous adhesions
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Vitreous floaters
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Lacrimation increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	6 / 103 (5.83%)
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	6
Ocular hyperaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1
Ocular surface disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Pinguecula
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Punctate keratitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 27 (3.70%)	1 / 8 (12.50%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	1	1	2	1	5
Retinal detachment
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	4	2	0	0	0
Subretinal fluid
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
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	3
Trichiasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	1	0	0	0	0	2
Vision blurred
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 7 (14.29%)	1 / 14 (7.14%)	8 / 57 (14.04%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	1 / 24 (4.17%)	1 / 27 (3.70%)	1 / 8 (12.50%)	4 / 19 (21.05%)	8 / 103 (7.77%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	1	1	1	8	0	1	0	1	1	1	4	9
Visual impairment
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	2	0	0	1	0	0	0	0	0	0	1	4
Vitreous detachment
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Xerophthalmia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Gastrointestinal disorders
Nausea
subjects affected / exposed	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	2 / 4 (50.00%)	3 / 8 (37.50%)	3 / 7 (42.86%)	1 / 4 (25.00%)	1 / 5 (20.00%)	4 / 14 (28.57%)	1 / 7 (14.29%)	5 / 14 (35.71%)	21 / 57 (36.84%)	4 / 34 (11.76%)	3 / 15 (20.00%)	4 / 13 (30.77%)	7 / 24 (29.17%)	13 / 27 (48.15%)	3 / 8 (37.50%)	8 / 19 (42.11%)	25 / 103 (24.27%)
occurrences all number	2	0	0	0	0	2	4	4	4	1	1	6	1	10	30	5	3	4	7	20	3	11	38
Oesophageal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Oral pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	2 / 13 (15.38%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	2	0	0	0	0	4
Rectal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	1 / 15 (6.67%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	1	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	5 / 14 (35.71%)	1 / 7 (14.29%)	3 / 14 (21.43%)	13 / 57 (22.81%)	3 / 34 (8.82%)	3 / 15 (20.00%)	2 / 13 (15.38%)	4 / 24 (16.67%)	2 / 27 (7.41%)	1 / 8 (12.50%)	7 / 19 (36.84%)	25 / 103 (24.27%)
occurrences all number	0	0	0	0	0	1	2	7	1	0	0	7	1	5	28	3	3	5	10	2	2	7	56
Vomiting
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	3 / 8 (37.50%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 5 (20.00%)	3 / 14 (21.43%)	2 / 7 (28.57%)	5 / 14 (35.71%)	15 / 57 (26.32%)	10 / 34 (29.41%)	1 / 15 (6.67%)	3 / 13 (23.08%)	5 / 24 (20.83%)	8 / 27 (29.63%)	0 / 8 (0.00%)	4 / 19 (21.05%)	20 / 103 (19.42%)
occurrences all number	0	0	0	0	0	0	2	4	2	0	1	4	4	7	31	14	2	3	12	13	0	5	30
Cheilitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Epigastric discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Haematemesis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oesophagitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Proctalgia
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Colonic pseudo-obstruction
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Gingival oedema
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Glossodynia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Proctitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Abdominal discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	1	0	1	0	2	0	1	1
Abdominal distension
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	2 / 14 (14.29%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	6 / 103 (5.83%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0	0	1	2	3	0	0	0	0	0	0	2	6
Abdominal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 5 (0.00%)	3 / 14 (21.43%)	1 / 7 (14.29%)	1 / 14 (7.14%)	15 / 57 (26.32%)	5 / 34 (14.71%)	3 / 15 (20.00%)	1 / 13 (7.69%)	5 / 24 (20.83%)	3 / 27 (11.11%)	0 / 8 (0.00%)	2 / 19 (10.53%)	21 / 103 (20.39%)
occurrences all number	0	0	0	1	0	0	1	1	2	0	0	6	1	1	22	5	3	1	9	3	0	2	28
Abdominal pain lower
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	0	0
Anal inflammation
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Ascites
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	1	0	0	0	4	5
Constipation
subjects affected / exposed	2 / 6 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	2 / 4 (50.00%)	4 / 8 (50.00%)	1 / 7 (14.29%)	1 / 4 (25.00%)	1 / 5 (20.00%)	5 / 14 (35.71%)	3 / 7 (42.86%)	7 / 14 (50.00%)	18 / 57 (31.58%)	9 / 34 (26.47%)	6 / 15 (40.00%)	3 / 13 (23.08%)	9 / 24 (37.50%)	11 / 27 (40.74%)	1 / 8 (12.50%)	8 / 19 (42.11%)	40 / 103 (38.83%)
occurrences all number	2	1	0	0	0	1	2	10	1	1	1	11	4	10	25	11	10	4	12	15	2	10	50
Diarrhoea
subjects affected / exposed	0 / 6 (0.00%)	3 / 3 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	2 / 4 (50.00%)	6 / 8 (75.00%)	3 / 7 (42.86%)	0 / 4 (0.00%)	0 / 5 (0.00%)	5 / 14 (35.71%)	3 / 7 (42.86%)	7 / 14 (50.00%)	17 / 57 (29.82%)	13 / 34 (38.24%)	4 / 15 (26.67%)	3 / 13 (23.08%)	11 / 24 (45.83%)	10 / 27 (37.04%)	5 / 8 (62.50%)	5 / 19 (26.32%)	37 / 103 (35.92%)
occurrences all number	0	3	3	0	1	1	5	7	6	0	0	9	3	10	19	16	7	4	17	14	7	7	65
Dry mouth
subjects affected / exposed	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 5 (0.00%)	3 / 4 (75.00%)	3 / 8 (37.50%)	2 / 7 (28.57%)	2 / 4 (50.00%)	1 / 5 (20.00%)	4 / 14 (28.57%)	1 / 7 (14.29%)	3 / 14 (21.43%)	13 / 57 (22.81%)	4 / 34 (11.76%)	3 / 15 (20.00%)	1 / 13 (7.69%)	3 / 24 (12.50%)	7 / 27 (25.93%)	0 / 8 (0.00%)	7 / 19 (36.84%)	36 / 103 (34.95%)
occurrences all number	3	3	1	2	0	0	3	3	3	2	1	4	1	3	15	4	4	1	3	7	0	7	41
Dyspepsia
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	3 / 34 (8.82%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	3 / 27 (11.11%)	0 / 8 (0.00%)	3 / 19 (15.79%)	7 / 103 (6.80%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	4	5	0	0	2	3	0	4	8
Dysphagia
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	5 / 103 (4.85%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	1	1	0	0	0	5
Flatulence
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	2 / 14 (14.29%)	7 / 57 (12.28%)	2 / 34 (5.88%)	2 / 15 (13.33%)	1 / 13 (7.69%)	3 / 24 (12.50%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	2	11	2	2	2	5	2	0	1	8
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Haemorrhoids
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	0	1	0	2
Lip swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (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
Mouth ulceration
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2	0	0	1	0	0	1	4
Abdominal pain upper
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 7 (14.29%)	1 / 14 (7.14%)	4 / 57 (7.02%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	3 / 27 (11.11%)	0 / 8 (0.00%)	3 / 19 (15.79%)	8 / 103 (7.77%)
occurrences all number	0	1	0	2	0	0	0	0	0	1	0	1	1	1	8	2	0	0	0	4	0	3	10
Intestinal obstruction
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hyperbilirubinaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6	0	1	0	0	2	0	0	5
Bile duct stenosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Bile duct obstruction
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hepatic pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	3 / 8 (37.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	1 / 7 (14.29%)	3 / 14 (21.43%)	18 / 57 (31.58%)	5 / 34 (14.71%)	3 / 15 (20.00%)	0 / 13 (0.00%)	5 / 24 (20.83%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	35 / 103 (33.98%)
occurrences all number	0	0	0	0	0	0	0	3	1	0	0	2	1	3	23	7	3	0	5	2	0	3	41
Blister
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1
Decubitus ulcer
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Dermatitis allergic
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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	2	0
Dermatitis contact
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	0 / 103 (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	2	0
Dry skin
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 7 (28.57%)	0 / 4 (0.00%)	1 / 5 (20.00%)	3 / 14 (21.43%)	0 / 7 (0.00%)	2 / 14 (14.29%)	11 / 57 (19.30%)	2 / 34 (5.88%)	1 / 15 (6.67%)	1 / 13 (7.69%)	3 / 24 (12.50%)	4 / 27 (14.81%)	0 / 8 (0.00%)	7 / 19 (36.84%)	30 / 103 (29.13%)
occurrences all number	1	0	0	1	1	1	0	1	2	0	1	3	0	2	11	3	1	1	3	5	0	7	39
Erythema
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0	0	0	0	2
Hypertrichosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	1	1	0	1	0	3	1
Itching scar
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Nail bed disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Nail discolouration
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	2 / 19 (10.53%)	14 / 103 (13.59%)
occurrences all number	1	0	0	0	0	0	0	1	1	0	0	0	0	0	4	1	0	1	0	0	1	2	20
Nail disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	2 / 14 (14.29%)	3 / 57 (5.26%)	0 / 34 (0.00%)	2 / 15 (13.33%)	0 / 13 (0.00%)	3 / 24 (12.50%)	3 / 27 (11.11%)	1 / 8 (12.50%)	1 / 19 (5.26%)	16 / 103 (15.53%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	2	5	0	2	0	7	3	1	1	20
Nail hypertrophy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	1	1
Nail ridging
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	1	0	0	1	0	1	0
Onychalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	3 / 57 (5.26%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	8	2	0	0	0	0	0	1	3
Onycholysis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	2 / 8 (25.00%)	2 / 7 (28.57%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	6 / 57 (10.53%)	1 / 34 (2.94%)	1 / 15 (6.67%)	0 / 13 (0.00%)	3 / 24 (12.50%)	2 / 27 (7.41%)	0 / 8 (0.00%)	3 / 19 (15.79%)	16 / 103 (15.53%)
occurrences all number	0	0	0	0	0	0	1	3	2	0	0	0	0	1	9	1	2	0	3	2	0	3	24
Onychomadesis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	15 / 103 (14.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0	0	3	19
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	1 / 14 (7.14%)	15 / 57 (26.32%)	2 / 34 (5.88%)	3 / 15 (20.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 27 (7.41%)	1 / 8 (12.50%)	6 / 19 (31.58%)	22 / 103 (21.36%)
occurrences all number	0	0	0	0	0	1	0	3	0	0	0	3	0	2	38	4	5	1	8	2	1	19	87
Palmoplantar keratoderma
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Papule
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Plantar erythema
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	2 / 27 (7.41%)	0 / 8 (0.00%)	1 / 19 (5.26%)	9 / 103 (8.74%)
occurrences all number	1	0	0	0	0	0	0	1	0	1	0	0	0	0	3	1	0	0	1	2	0	1	12
Rash
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	5 / 103 (4.85%)
occurrences all number	1	0	1	1	0	2	0	1	0	0	1	0	0	0	2	0	1	0	2	1	0	5	6
Rash maculo-papular
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	2	0	0	2	1	0	0	4
Skin hypertrophy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	0 / 103 (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	2	0
Skin mass
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0
Swelling face
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (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	1	0	0
Xeroderma
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (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
Skin ulcer
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Skin haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Skin fissures
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash macular
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Night sweats
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Nail dystrophy
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Nail bed tenderness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Onychoclasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pain of skin
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Urticaria
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Urticaria contact
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hyperhidrosis
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Skin exfoliation
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dermatitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	1
Bladder prolapse
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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	2	0
Dysuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	1 / 15 (6.67%)	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	5 / 103 (4.85%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	2	0	0	1	0	1	1	1	1	0	0	5
Haematuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	2 / 15 (13.33%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	2	0	0	0	0	1	3
Pollakiuria
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	3
Proteinuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0	0	0	4
Renal failure
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1	0
Urinary retention
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1
Micturition disorder
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hypopituitarism
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	10 / 57 (17.54%)	3 / 34 (8.82%)	1 / 15 (6.67%)	2 / 13 (15.38%)	2 / 24 (8.33%)	2 / 27 (7.41%)	1 / 8 (12.50%)	3 / 19 (15.79%)	23 / 103 (22.33%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	1	0	0	20	5	1	3	2	2	1	3	32
Bone pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1
Joint swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	2	0	0	2
Muscular weakness
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	4 / 34 (11.76%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	5	1	0	0	0	0	0	3
Musculoskeletal chest pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	2 / 19 (10.53%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	2	0	2	2
Musculoskeletal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	2 / 57 (3.51%)	1 / 34 (2.94%)	0 / 15 (0.00%)	1 / 13 (7.69%)	2 / 24 (8.33%)	0 / 27 (0.00%)	0 / 8 (0.00%)	3 / 19 (15.79%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	1	2	2	0	1	2	0	0	3	8
Myalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	4 / 57 (7.02%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	0 / 19 (0.00%)	15 / 103 (14.56%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	8	0	1	0	0	2	0	0	24
Neck pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0	0	0	1	0	0	0	2	1
Pain in extremity
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	1 / 14 (7.14%)	3 / 57 (5.26%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	1 / 27 (3.70%)	0 / 8 (0.00%)	5 / 19 (26.32%)	9 / 103 (8.74%)
occurrences all number	0	0	0	1	0	0	0	2	0	0	1	0	1	1	10	2	0	1	2	1	0	10	13
Tendonitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	1 / 8 (12.50%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0
Dactylitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Groin pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Osteolysis
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Pain in jaw
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Flank pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Back pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	1 / 5 (20.00%)	1 / 14 (7.14%)	2 / 7 (28.57%)	1 / 14 (7.14%)	6 / 57 (10.53%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	1 / 27 (3.70%)	1 / 8 (12.50%)	5 / 19 (26.32%)	17 / 103 (16.50%)
occurrences all number	1	0	0	1	0	0	0	1	0	0	1	1	2	1	8	3	0	0	3	1	2	6	21
Muscle spasms
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	2 / 14 (14.29%)	0 / 7 (0.00%)	1 / 14 (7.14%)	5 / 57 (8.77%)	3 / 34 (8.82%)	2 / 15 (13.33%)	1 / 13 (7.69%)	1 / 24 (4.17%)	2 / 27 (7.41%)	0 / 8 (0.00%)	2 / 19 (10.53%)	15 / 103 (14.56%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	1	8	3	3	1	1	2	0	3	21
Musculoskeletal stiffness
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Infections and infestations
Bacteraemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
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	1
Bronchitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	1	0	0	0
Cellulitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	3 / 57 (5.26%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0	0	0	1	3	0	0	1	0	1	0	0	3
Cellulitis staphylococcal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0	0	1	0
Conjunctivitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	2 / 57 (3.51%)	2 / 34 (5.88%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	2	2	0	0	0	1	0	0	3
Cystitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
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	2
Device related infection
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	1 / 103 (0.97%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Gastroenteritis viral
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0
Herpes zoster
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	1 / 8 (12.50%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1	1	0
Influenza
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	0 / 103 (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	2	0
Lower respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	1	0	0
Lung infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 27 (0.00%)	1 / 8 (12.50%)	0 / 19 (0.00%)	2 / 103 (1.94%)
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	2
Oral candidiasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2	2
Otitis media
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
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
Paronychia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	1 / 34 (2.94%)	1 / 15 (6.67%)	1 / 13 (7.69%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	5 / 19 (26.32%)	8 / 103 (7.77%)
occurrences all number	0	0	0	0	0	0	0	2	1	0	0	6	0	0	8	2	1	1	1	0	0	8	18
Pharyngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	1	2
Pharyngitis streptococcal
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Sinusitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	2 / 57 (3.51%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	0	1	2
Tooth infection
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	4 / 57 (7.02%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	1 / 19 (5.26%)	7 / 103 (6.80%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	4	0	0	0	0	2	0	1	7
Urinary tract infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 4 (50.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	5 / 57 (8.77%)	2 / 34 (5.88%)	3 / 15 (20.00%)	0 / 13 (0.00%)	2 / 24 (8.33%)	3 / 27 (11.11%)	2 / 8 (25.00%)	6 / 19 (31.58%)	20 / 103 (19.42%)
occurrences all number	0	1	2	0	0	0	2	1	0	0	0	0	0	0	9	3	4	0	2	5	3	7	23
Urosepsis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	1 / 103 (0.97%)
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
Pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	1	0	1	0	1	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Folliculitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Localised infection
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Onychomycosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Sepsis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oral fungal infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Vaginal infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Bronchitis viral
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Oesophageal candidiasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Pelvic abscess
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Stoma site infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Metabolism and nutrition disorders
Calciphylaxis
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	0 / 103 (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
Decreased appetite
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	3 / 8 (37.50%)	2 / 7 (28.57%)	1 / 4 (25.00%)	2 / 5 (40.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	3 / 14 (21.43%)	10 / 57 (17.54%)	6 / 34 (17.65%)	4 / 15 (26.67%)	1 / 13 (7.69%)	7 / 24 (29.17%)	6 / 27 (22.22%)	1 / 8 (12.50%)	3 / 19 (15.79%)	23 / 103 (22.33%)
occurrences all number	0	1	0	2	0	0	1	3	4	2	3	1	0	3	11	6	7	1	12	8	1	4	51
Dehydration
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	2 / 19 (10.53%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	1	0	0	1	0	0	0	0	2	0	2	12
Hypercalcaemia
subjects affected / exposed	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	12 / 57 (21.05%)	2 / 34 (5.88%)	2 / 15 (13.33%)	2 / 13 (15.38%)	1 / 24 (4.17%)	4 / 27 (14.81%)	0 / 8 (0.00%)	4 / 19 (21.05%)	16 / 103 (15.53%)
occurrences all number	1	1	0	1	0	0	2	6	0	0	0	0	0	0	19	5	3	3	2	6	0	6	30
Hyperglycaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	3 / 57 (5.26%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	2 / 27 (7.41%)	0 / 8 (0.00%)	2 / 19 (10.53%)	4 / 103 (3.88%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	5	1	0	0	0	3	0	4	5
Hyperkalaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	1 / 57 (1.75%)	1 / 34 (2.94%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	1 / 19 (5.26%)	3 / 103 (2.91%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	1	0	0	3	1	0	0	0	0	0	3	5
Hyperphosphataemia
subjects affected / exposed	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	4 / 5 (80.00%)	3 / 4 (75.00%)	6 / 8 (75.00%)	6 / 7 (85.71%)	1 / 4 (25.00%)	2 / 5 (40.00%)	9 / 14 (64.29%)	6 / 7 (85.71%)	12 / 14 (85.71%)	48 / 57 (84.21%)	30 / 34 (88.24%)	9 / 15 (60.00%)	12 / 13 (92.31%)	19 / 24 (79.17%)	21 / 27 (77.78%)	5 / 8 (62.50%)	17 / 19 (89.47%)	88 / 103 (85.44%)
occurrences all number	0	1	3	0	0	7	6	16	10	1	2	11	7	33	220	108	22	36	74	58	19	71	537
Hyperuricaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	1 / 34 (2.94%)	0 / 15 (0.00%)	2 / 13 (15.38%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0	15
Hypocalcaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	0 / 19 (0.00%)	2 / 103 (1.94%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	1	0	0	2
Hypokalaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	6 / 57 (10.53%)	2 / 34 (5.88%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	3 / 27 (11.11%)	0 / 8 (0.00%)	0 / 19 (0.00%)	6 / 103 (5.83%)
occurrences all number	0	0	0	0	0	2	1	1	0	1	0	1	0	0	6	4	0	1	0	4	0	0	10
Hypomagnesaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 5 (40.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	1 / 14 (7.14%)	1 / 57 (1.75%)	0 / 34 (0.00%)	0 / 15 (0.00%)	1 / 13 (7.69%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	3 / 19 (15.79%)	3 / 103 (2.91%)
occurrences all number	1	0	0	1	0	3	0	0	0	1	0	1	0	1	1	0	0	1	0	0	0	3	3
Hyponatraemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 5 (20.00%)	2 / 4 (50.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	1 / 4 (25.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	1 / 7 (14.29%)	1 / 14 (7.14%)	3 / 57 (5.26%)	1 / 34 (2.94%)	1 / 15 (6.67%)	2 / 13 (15.38%)	0 / 24 (0.00%)	1 / 27 (3.70%)	0 / 8 (0.00%)	3 / 19 (15.79%)	17 / 103 (16.50%)
occurrences all number	1	0	0	1	0	8	4	1	1	1	0	1	2	1	4	2	1	3	0	2	0	4	32
Hypophosphataemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	1 / 7 (14.29%)	0 / 14 (0.00%)	10 / 57 (17.54%)	2 / 34 (5.88%)	0 / 15 (0.00%)	2 / 13 (15.38%)	1 / 24 (4.17%)	0 / 27 (0.00%)	0 / 8 (0.00%)	2 / 19 (10.53%)	14 / 103 (13.59%)
occurrences all number	0	0	0	0	0	0	0	4	0	0	0	0	1	0	22	2	0	3	2	0	0	2	21
Hypovolaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	1 / 15 (6.67%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Failure to thrive
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 4 (0.00%)	0 / 5 (0.00%)	0 / 14 (0.00%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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
Hypophagia
subjects affected / exposed	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 4 (0.00%)	0 / 5 (0.00%)	1 / 14 (7.14%)	0 / 7 (0.00%)	0 / 14 (0.00%)	0 / 57 (0.00%)	0 / 34 (0.00%)	0 / 15 (0.00%)	0 / 13 (0.00%)	0 / 24 (0.00%)	0 / 27 (0.00%)	0 / 8 (0.00%)	0 / 19 (0.00%)	0 / 103 (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

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Were there any global substantial amendments to the protocol? Yes

31 Jan 2014

- Added language “who have failed all standard therapies or for whom standard therapy does not exist” in order to clarify study rationale, study objectives, study design, and inclusion criteria (Phase 1 Dose Escalation) - Revised “Definitions of Dose-limiting Toxicity and Maximum Tolerated Dose” criteria for hyperphosphatemia and increase of creatinine. - Revised inclusion criteria to include serum phosphorus and serum calcium - Revised exclusion criteria to include QT interval - Added information to management of hyperphosphatemia - Added ophthalmological examination visits per local requirement or as clinically indicated

22 Sep 2014

- Updated visit schedules in Table 1A and Table 1B (serum chemistry only) - Added information to the exclusion criteria for noninvestigational anticancer therapy - Expanded the list of concomitant medications and therapies - Revised “Definitions of Dose-limiting Toxicity and Maximum Tolerated Dose” criteria for hyperphosphatemia and creatinine increase. - Added serum phosphorus and serum calcium to inclusion criteria - Added information to the QT interval exclusion criteria - Clarified management of hyperphosphatemia - Revised dose reduction requirements - Clarified Screening criteria - Clarified fractionation of CK into isoforms - Clarified postdose blood sample collection (QOD and QD) pharmacokinetics (PK)/pharmacodynamic collection (Phase 1 Dose Escalation). - Clarified of postdose urine sample (QOD only) urine sample to pharmacodynamic urine sample collection (Phase 1 Dose Escalation). - Clarification of study phase to solid tumor assessments/scans - Expanded method of capturing and reporting medication errors.

19 Feb 2016

- Removed references to NSCLC, gastric, and breast cancers and multiple myeloma population from sections throughout the protocol amendment as appropriate - Added information to timing of initiating the QD arm in relation to QOD dosing schedule - Updated the language on women of childbearing potential and effective contraception inclusion criteria to comply with Clinical Trials Facilitation Group (CTFG) Guidelines - Added change to include tablets (i.e., number of tablets, description of packaging and storage information) about 4 mg and 20 mg TAS-120 tablets. - Updated information on assessment of overall response rate - Revised section on determination of sample size - Updated guidelines for management of hyperphosphatemia - Added additional electrocardiogram (ECG) evaluations as appropriate

15 May 2017

- Updated clinical information for 2 clinical trials TAS-120-101 Phase 1/2 Trial TPU-TAS-120-101 [US/EU/Australia] and Phase 1 trial 10059010 [Japan] - Added rationale for the selection of QD dosing schedule - Added a new intermediate dose level of 20 mg QD to enable a more precise determination of the Recommended Phase 2 Dose (RP2D)

29 Aug 2017

- Added specific cohorts of patients to be enrolled in the 4 groups in the Phase 1 Expansion - Updated study endpoints for the Phase 1 Expansion and Phase 2 parts of the study including early progression rate (EPR) as a primary endpoint and added Response Assessment in Neuro-Oncology (RANO) as the guidelines for efficacy assessment for patients with glioblastoma multiforme (GBM) or grade III glioma, PFS and OS. - Added efficacy and tumor assessments for brain tumors and added RANO tumor assessment criteria for brain tumors. - Updated the inclusion and exclusion criteria to further define patients included in Phase 1 Expansion and Phase 2 - Revised guidelines for serum phosphorus monitoring and management of hyperphosphatemia - Provided the procedure for screening and identifying iCCA patients with tumors that have FGFR gene fusions in the Phase 2 part of the study. - Added assessment of CA19-9 for cholangiocarcinoma patients - Clarification of evaluations at visit schedules - Updated definitions of populations in statistical methods in both the Phase 1 Expansion and Phase 2 - Revised section on determination of sample size to further specify the sample size justification for the specific cohorts of patients to be enrolled in the Phase 1 Expansion and to provide sample size justification for patients enrolled in the Phase 2 part of the study.

31 Jan 2018

- Added an additional 4 cohorts of patients to be enrolled in the Phase 1 Expansion. - Added information that established 20 mg QD as the RP2D - Clarified Phase 2 primary objective, added a key secondary objective, other secondary objectives and PK exploratory objective - Updated the inclusion and exclusion criteria to further define patients in Phase 1 Expansion and Phase 2 - Provided methods for prescreening testing of tumor samples for FGFR2 gene fusion before enrollment into Phase 2 - Removed TAS-120 capsule formulation as it is no longer applicable - Updated information on timing and fasting requirements to study drug administration procedures - Updated guidelines on Dose Hold, Dose Modifications and Dose Resumption - Clarification of evaluations in visit schedules - Updated information on statistical analysis of disease control rate (DCR), duration of response (DOR), PFS - Added assessments of and statistical analysis of Patient-Reported Outcome assessments. - Updated determination of sample size information to further specify the sample size justification for the specific cohorts of patients to be enrolled in the Phase 1 Expansion and to further specify sample size justification for patients enrolled in the Phase 2 part of the study.

28 Sep 2018

Global - Reformatted and clarified study events tables to ensure consistency throughout the protocol. - Altered inclusion requirement for bilirubin to allow for serum or plasma assessment of bilirubin and to include patients with Gilbert’s syndrome and bilirubin up to 3 x upper limit of normal. - Clarified requirements for pregnancy testing of women of childbearing potential throughout the study. - Throughout the document, editorial changes, including elimination of errors or minor rewordings to improve clarity, were made as necessary. The administrative alterations do not affect the planned conduct or analysis of the study. Phase I Expansion - Added brief rationale for the design of the Phase I expansion portion of the study. - Enrollment suspended into Phase I expansion Groups 1, 3, 4, 6, and 8. - Refined criteria for enrollment into other groups in Phase I expansion, including: o Changing the FGFR requirement for Group 7 from “FGF9 or FGF19 amplifications” to “FGFR2 amplifications.” o Changing the requirement for Group 5 from “grade III glioma” to “primary CNS tumors.” - Changes were made to study objectives, statistical methods, and other sections of the protocol as necessary for consistency with the revised population of each subgroup in the Phase I expansion portion of the study. Phase 2 - Expanded eligibility requirements to allow all patients with FGFR2 rearrangements, rather than patients with FGFR2 gene fusions only. - Clarified requirements for tumor testing to determine and/or confirm study eligibility on the basis of FGR2 gene fusion status. - Clarified requirements for prior therapy (patients must have received at least one prior systemic gemcitabine-platinum therapy and have documented progression following the most recent prior therapy. - Added planned interim reviews of safety to be performed approximately every 3 months throughout the study, including brief description of the SRC that will perform these reviews

12 Apr 2019

- Guidelines for management of hyperphosphatemia were updated to reflect analysis of most current available data.

01 Aug 2019

- Requirement to have FGFR2 rearrangements be centrally confirmed prior to enrollment was removed. - Interim analysis was added.

12 Feb 2021

- Table of list of evaluations to be performed during Study Extension. - Clinical experience with TAS-120 was updated. - Added definition of study completion. - The drug interactions with TAS-120 have been updated. - Study Extension was added to allow patients still receiving benefits to continue to receive TAS-120 after the study is considered complete. - Supplemental Requirements for Japan Only: The anticipated date of study completion was amended from April 2021 to July 2021.

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1: Dose Escalation- MTD

Primary: Phase 1: Dose Escalation- MTD

Primary: Phase 1: Dose Escalation- RP2D of TAS-120

Primary: Phase 1: Dose Escalation- RP2D of TAS-120

Primary: Phase 1: Dose Expansion: Percentage of Subjects With Objective Response

Primary: Phase 1: Dose Expansion: Percentage of Subjects With Objective Response

Primary: Phase 2: Percentage of Subjects With Objective Response

Primary: Phase 2: Percentage of Subjects With Objective Response

Secondary: Phase 1: Dose Expansion: Duration of Response (DOR)

Secondary: Phase 1: Dose Expansion: Duration of Response (DOR)

Secondary: Phase 2: Duration of Response (DOR)

Secondary: Phase 2: Duration of Response (DOR)

Secondary: Phase 1: Dose Expansion: Disease Control Rate (DCR)

Secondary: Phase 1: Dose Expansion: Disease Control Rate (DCR)

Secondary: Phase 2: Disease Control Rate (DCR)

Secondary: Phase 2: Disease Control Rate (DCR)

Secondary: Phase 1: Dose Expansion: Progression-free Survival (PFS)

Secondary: Phase 1: Dose Expansion: Progression-free Survival (PFS)

Secondary: Phase 2: Progression-free Survival (PFS)

Secondary: Phase 2: Progression-free Survival (PFS)

Secondary: Phase 1: Dose Expansion: Overall Survival (OS)

Secondary: Phase 1: Dose Expansion: Overall Survival (OS)

Secondary: Phase 2: Overall Survival (OS)

Secondary: Phase 2: Overall Survival (OS)

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Self-care Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Usual Activities Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Pain/Discomfort Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits

Secondary: Phase 2: European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Anxiety/Depression Scores at Specified Visits

Secondary: Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits

Secondary: Phase 2: Change From Baseline in EQ-5D-3L Visual Analogue Scale (VAS) at Specified Visits

Secondary: Phase 2: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints

Secondary: Phase 2: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score at Specified Timepoints

Secondary: Phase 1: Dose Expansion: Number of Subjects with Any Adverse Events (AEs) and Any Serious AEs (SAEs)

Secondary: Phase 1: Dose Expansion: Number of Subjects with Any Adverse Events (AEs) and Any Serious AEs (SAEs)

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

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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations