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Clinical Trial Results:
First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors

Summary
EudraCT number	2016-002243-42
Trial protocol	DK
Global end of trial date	12 Nov 2021

Results information
Results version number	v1(current)
This version publication date	15 Dec 2022
First version publication date	15 Dec 2022
Other versions

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

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Trial information

Top of page

Sponsor protocol code

GCT1021-01

ISRCTN number

US NCT number

NCT02988817

WHO universal trial number (UTN)

Sponsor organisation name

Genmab A/S

Sponsor organisation address

Kalvebod Brygge 43, Copenhagen V, Denmark, 1560

Public contact

Clinical Trial Information, Genmab A/S, +45 7020 2728, clinicaltrials@genmab.com

Scientific contact

Clinical Trial Information, Genmab A/S, +45 7020 2728, clinicaltrials@genmab.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

25 Feb 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

12 Nov 2021

Was the trial ended prematurely?

Main objective of the trial

The main objective of the study was to determine the maximum tolerated dose (MTD) and to establish the safety profile of enapotamab vedotin in a mixed population of participants with specified solid tumors.

Protection of trial subjects

The trial was conducted in accordance with the protocol and amendments, the International Council for Harmonisation E6 guideline for Good Clinical Practice, applicable local regulations, and ethical principles that have their origins in the Declaration of Helsinki. In addition, the trial was conducted in accordance with FDA 21 Code of Federal Regulations parts 312, 50, and 56, and the directive 2001/20/EC of the European Parliament.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Nov 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 29

Country: Number of subjects enrolled

Spain: 3

Country: Number of subjects enrolled

United Kingdom: 69

Country: Number of subjects enrolled

Belgium: 48

Country: Number of subjects enrolled

Denmark: 30

Country: Number of subjects enrolled

United States: 127

Worldwide total number of subjects

306

EEA total number of subjects

110

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)

180

From 65 to 84 years

126

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

This study was conducted in 6 countries (Belgium, Denmark, Spain, the United Kingdom, Netherlands, and the United States).

Period 1 title

Overall period

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.3 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 0.3 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 0.6 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.0 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.5 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.5 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.0 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.0 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.4 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.4 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 0.6 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.8 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 0.8 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.0 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Arm description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.2 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.2 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic NSCLC with classical sensitizing epidermal growth factor receptor (EGFR) mutations and/or EGFR mutations targeted by third-generation tyrosine kinase inhibitors, received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic melanoma with BRAF V600 mutation received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic melanoma with BRAF V600 wild type received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic sarcoma received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Arm description

Participants with advanced and/or metastatic solid tumors (excluding NSCLC, melanoma, sarcoma, and ovarian cancer unless having a known AXL gene amplification) received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.0 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic platinum-resistant ovarian cancer received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangements received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 2.2 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Arm description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.8 mg/kg 1Q3W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.8 mg/kg was administered intravenously every 3 weeks over a 21-day treatment cycle.

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Arm description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Arm type

Experimental

Investigational medicinal product name

Enapotamab vedotin

Investigational medicinal product code

Not applicable

Other name

HuMax®-AXL-ADC

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Enapotamab vedotin 1.0 mg/kg was administered intravenously every week for 3 weeks followed by 1 week without dosing over a 28-day treatment cycle.

Number of subjects in period 1	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W
Started	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	55	21	26
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	55	21	26
Adverse event, serious fatal	-	-	-	-	-	2	-	-	-	-	1	2	-	4	1	4	2	8	-	5
Consent withdrawn by subject	1	-	-	1	3	1	2	1	1	1	1	12	6	6	4	5	4	11	4	2
Physician decision	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1	-	-	1	1
Death	-	1	3	1	6	8	1	2	1	5	-	6	9	13	17	26	15	30	14	11
Unspecified	-	-	-	1	1	-	-	-	-	-	-	-	-	-	-	1	-	-	-	-
Lost to follow-up	-	-	-	-	-	-	-	-	1	-	1	1	-	-	1	1	2	3	-	-
Sponsor decision	-	-	-	-	-	-	-	-	-	-	-	1	1	2	2	6	2	3	2	7

Baseline characteristics

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Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.3 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.5 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.4 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.8 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.2 mg/kg 3Q4W until the end of treatment.

Reporting group title

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Reporting group title

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 mutation received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 wild type received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic sarcoma received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Reporting group title

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic platinum-resistant ovarian cancer received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.8 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Reporting group values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Total
Number of subjects	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	55	21	26	306
Age categorical
The data for 'Age categorical' are reported for participants from the full analysis set, which included all participants who received at least 1 dose of enapotamab vedotin and were analysed according to the assigned treatment/dose (planned dose level and schedule).
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	1	0	2	2	9	5	2	1	2	4	3	12	14	13	15	23	16	24	15	17	180
From 65-84 years	0	1	1	1	1	6	1	2	1	2	0	10	2	12	10	21	9	31	6	9	126
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gender categorical
The data for 'Gender categorical' are reported for participants from the full analysis set, which included all participants who received at least 1 dose of enapotamab vedotin and were analysed according to the assigned treatment/dose (planned dose level and schedule).
Units: Subjects
Female	1	1	3	3	7	10	3	2	2	6	3	13	8	7	14	17	25	25	11	13	174
Male	0	0	0	0	3	1	0	1	1	0	0	9	8	18	11	27	0	30	10	13	132

End points

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Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.3 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.5 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.4 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.8 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.2 mg/kg 3Q4W until the end of treatment.

Reporting group title

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Reporting group title

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 mutation received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 wild type received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic sarcoma received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Reporting group title

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic platinum-resistant ovarian cancer received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.8 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Subject analysis set title

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Subject analysis set type

Safety analysis

Subject analysis set description

The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified and were classified according to first dose received.

Subject analysis set title

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Subject analysis set type

Safety analysis

Subject analysis set description

Primary: Number of Participants With Dose-limiting Toxicities (DLTs) for Dose-escalation Part

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End point title

Number of Participants With Dose-limiting Toxicities (DLTs) for Dose-escalation Part ^[1] ^[2]

End point description

The DLTs were defined as Grade (G)4 neutropenia or G4 thrombocytopenia for <=7 days, G3/G4 febrile neutropenia, >=G3 hemorrhage with >=G3 thrombocytopenia, G4 anemia; Stevens Johnson syndrome, toxic epidermal necrolysis, >=G3 cutaneous vasculitis; G3 neuropathy (not improved to G1 within 3 weeks after dose stop), G4 neuropathy; G3 infusion-related reactions (IRR) not resolved to G1/baseline <24 hours; G4 IRR/G4 anaphylaxis events; >= G3 diarrhoea and/or vomiting persisting >48 hours or G3 nausea lasting 7 days (both despite optimal medical management); or any >=G3 related non-hematological AEs, occurred during Cycle 1 and regarded as medically important by Data Monitoring Committee (excluding Grade 3 fatigue or non-hematological laboratory abnormalities). Dose-determining set included participants from Safety set who received at least 1 dose of enapotamab vedotin and either met minimum exposure criterion and completed DLT observation period, or who experienced a DLT during Cycle 1.

End point type

Primary

End point timeframe

From Day 1 to Day 21 of first cycle for 1Q3W dosing regimen and from Day 1 to Day 28 of first cycle for 3Q4W dosing regimen

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	10	3	3	3	6	2
Units: Participants	0	0	0	0	1	2	1	0	0	0	2

No statistical analyses for this end point

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

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End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) ^[3] ^[4]

End point description

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is defined as an AE that meets one of the following criteria: requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, is a congenital anomaly/birth defect, is medically important, results in death, or is life-threatening. In this trial, a TEAE was defined as an AE occurring or worsening between the first dose of enapotamab vedotin and 30 days after the last dose received. The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified according to first dose received.

End point type

Primary

End point timeframe

Day 1 through Day 1130 (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Units: Participants
Any TEAE	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Any TESAE	0	0	0	2	7	6	2	1	0	2	3	15	5	16	10	16	12	14	33	7

No statistical analyses for this end point

Primary: Number of Participants With Treatment-emergent Infusion-related AEs and TEAEs Related to Enapotamab Vedotin

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End point title

Number of Participants With Treatment-emergent Infusion-related AEs and TEAEs Related to Enapotamab Vedotin ^[5] ^[6]

End point description

Number of participants with treatment-emergent infusion-related AEs and TEAEs related to enapotamab vedotin is reported. The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified according to first dose received.

End point type

Primary

End point timeframe

Day 1 through Day 1130 (maximum observed duration)

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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed 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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Units: Participants
Treatment emergent infusion-related AEs	0	0	0	1	0	0	0	0	2	1	0	0	0	1	2	2	0	0	2	1
TEAEs related to enapotamab vedotin	1	1	3	3	10	10	3	3	3	6	3	21	15	24	24	38	23	20	52	16

No statistical analyses for this end point

Primary: Number of Participants With >= Grade 3 TEAEs as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

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End point title

Number of Participants With >= Grade 3 TEAEs as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 ^[7] ^[8]

End point description

Number of participants with TEAEs of >= Grade 3 as assessed by NCI-CTCAE v4.03 is reported. The NCI-CTCAE is a descriptive terminology is used for AE reporting. The NCI-CTCAE v4.03 displays Grades 1 through 5 with unique clinical descriptions of severity for each AE, based on this general guideline: Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as life-threatening or disabling AE, and Grade 5 as death. If a participant reported multiple severity grades for an AE, only the maximum grade was used. The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified according to first dose received.

End point type

Primary

End point timeframe

Day 1 through Day 1130 (maximum observed duration)

Notes
[7] - 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: Statistical analysis was not applicable since there were no inferential statistics, only descriptive statistics were performed for this end point.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Units: Participants	0	0	0	2	7	9	3	1	0	3	3	15	6	18	16	21	15	13	40	14

No statistical analyses for this end point

Secondary: Number of Participants With Grade 3 or 4 Laboratory Results

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End point title

Number of Participants With Grade 3 or 4 Laboratory Results ^[9]

End point description

Number of participants with laboratory measurements graded as Grade 3 or 4 by NCI-CTCAE v 4.03 is reported. The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified according to first dose received.

End point type

Secondary

End point timeframe

Day 1 through Day 1130 (maximum observed duration)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Units: Participants
Activated partial thromboplastin time	0	0	0	0	0	1	1	0	0	0	0	0	0	0	0	1	0	0	2	0
Alanine aminotransferase	0	1	0	0	0	1	0	0	0	0	0	0	0	1	1	0	0	1	2	0
Amylase	0	0	0	0	1	0	0	0	0	0	0	0	0	1	1	1	1	1	2	0
Aspartate aminotransferase	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	2	0
Calcium	0	0	0	0	1	0	1	0	0	0	1	0	0	0	0	1	0	1	0	0
Gamma-glutamyl transferase	0	1	0	0	1	4	1	0	1	1	2	5	0	3	0	7	4	3	8	1
Leukocytes	0	0	0	0	1	0	0	0	0	0	0	0	0	2	3	2	1	1	2	2
Lipase	0	0	0	0	1	0	1	0	0	0	0	5	1	2	1	1	3	1	4	3
Lymphocytes	1	0	0	0	2	2	0	0	1	2	0	5	0	5	7	9	8	4	9	2
Magnesium	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	2	1	0
Neutrophils	0	0	0	0	4	0	1	0	0	0	0	1	1	4	7	3	5	2	8	2
Potassium	0	0	0	0	1	1	0	0	1	1	0	0	0	1	1	1	0	1	1	0
Prothrombin Intl. Normalized Ratio	0	0	1	0	0	1	0	0	0	0	0	1	0	0	0	1	2	1	4	0
Sodium	0	0	0	0	1	3	1	0	0	0	0	1	1	1	4	2	3	3	7	1
Triglycerides	0	0	0	0	1	1	0	0	0	2	1	0	2	2	3	1	1	0	1	0
Alkaline Phosphatase	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	1	0	1	1	0
Hemoglobin	0	0	0	0	0	0	0	0	0	1	0	1	0	1	1	3	1	0	2	0
Albumin	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Bilirubin	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Cholesterol	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[10]

End point description

The AUC0-inf of conjugated enapotamab vedotin for dose-escalation part is reported. The pharmacokinetic (PK) analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here, 'n' denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

Predose, end of infusion (EOI), and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3
Units: day*ug/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n = 1, 1, 3, 3, 10, 10, 3)	6.143 ( 99999.0 )	13.233 ( 99999.0 )	18.353 ( 8.6 )	40.921 ( 27.7 )	64.140 ( 13.2 )	67.998 ( 32.2 )	76.264 ( 31.7 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0)	5.780 ( 99999.0 )	10.892 ( 99999.0 )	18.664 ( 99999.0 )	39.589 ( 99999.0 )	56.842 ( 23.8 )	61.161 ( 10.7 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[11]

End point description

The AUC0-last of conjugated enapotamab vedotin for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here, 'n' denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3
Units: day*ug/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n = 1, 1, 3, 3, 10, 10, 3)	5.509 ( 99999.0 )	10.369 ( 99999.0 )	16.004 ( 18.5 )	36.526 ( 29.7 )	58.410 ( 11.6 )	62.563 ( 29.7 )	71.196 ( 32.5 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0)	5.306 ( 99999.0 )	9.157 ( 99999.0 )	15.047 ( 99999.0 )	36.333 ( 99999.0 )	51.541 ( 21.4 )	57.759 ( 11.9 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Maximum Observed Plasma Concentration (Cmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Maximum Observed Plasma Concentration (Cmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[12]

End point description

The Cmax of conjugated enapotamab vedotin for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here, 'n' denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose and EOI on Days 1 and 8 of Cycles 1 and 3; and predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: ug/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n =1, 1, 3, 3, 10, 10, 3, 3, 2, 6, 3)	7.250 ( 99999.0 )	12.600 ( 99999.0 )	16.615 ( 16.7 )	33.005 ( 9.4 )	39.647 ( 11.4 )	43.377 ( 25.6 )	48.548 ( 33.0 )	10.127 ( 40.2 )	14.307 ( 31.6 )	18.040 ( 12.0 )	17.928 ( 22.0 )
Cycle1 Day8 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 3)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	14.201 ( 11.9 )	16.765 ( 36.3 )	18.698 ( 8.1 )	18.958 ( 19.5 )
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	13.172 ( 8.0 )	16.166 ( 37.2 )	16.991 ( 7.8 )	18.500 ( 99999.0 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0, 0, 1, 1, 0)	6.870 ( 99999.0 )	11.000 ( 99999.0 )	16.200 ( 99999.0 )	32.400 ( 99999.0 )	35.890 ( 17.9 )	38.928 ( 9.0 )	0 ( 0 )	0 ( 0 )	22.400 ( 99999.0 )	21.800 ( 99999.0 )	0 ( 0 )
Cycle3 Day8 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	21.200 ( 99999.0 )	0 ( 0 )	0 ( 0 )
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	24.100 ( 99999.0 )	22.800 ( 99999.0 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Total Clearance (CL) of Conjugated Enapotamab Vedotin in Dose-escalation Part

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End point title

Total Clearance (CL) of Conjugated Enapotamab Vedotin in Dose-escalation Part ^[13]

End point description

The total CL of conjugated enapotamab vedotin in dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: L/day
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n = 1, 1, 3, 3, 10, 10, 3, 0, 0, 0, 0	4.053 ( 99999.0 )	3.446 ( 99999.0 )	3.538 ( 21.8 )	2.307 ( 28.3 )	2.202 ( 22.2 )	2.205 ( 25.4 )	1.783 ( 24.3 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	3.679 ( 9.4 )	3.084 ( 93.8 )	3.402 ( 31.3 )	2.629 ( 99999.0 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0, 0, 0, 0, 0)	4.360 ( 99999.0 )	4.187 ( 99999.0 )	3.000 ( 99999.0 )	2.160 ( 99999.0 )	2.285 ( 27.1 )	2.539 ( 14.7 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	2.281 ( 99999.0 )	2.281 ( 99999.0 )	3.412 ( 99999.0 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Time of Maximum Plasma Concentration (Tmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Time of Maximum Plasma Concentration (Tmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[14]

End point description

The Tmax of conjugated enapotamab vedotin for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: Day
median (full range (min-max))
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 3, 0, 0, 0, 0)	0.06 (0.06 to 0.06)	0.03 (0.03 to 0.03)	0.036 (0.03 to 0.04)	0.033 (0.03 to 0.04)	0.032 (0.02 to 0.09)	0.032 (0.02 to 0.04)	0.03 (0.02 to 0.03)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	14.010 (13.96 to 14.88)	14.058 (13.98 to 14.08)	14.083 (14.00 to 14.19)	13.98 (13.98 to 13.98)
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0, 0, 0, 0, 0)	0.04 (0.04 to 0.04)	0.03 (0.03 to 0.03)	0.04 (0.04 to 0.04)	0.030 (0.03 to 0.03)	0.036 (0.02 to 0.05)	0.042 (0.03 to 0.11)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	14.02 (14.02 to 14.02)	13.98 (13.98 to 13.98)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Half-life Lambda-z (t1/2) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Half-life Lambda-z (t1/2) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[15]

End point description

The t1/2 of conjugated enapotamab vedotin for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: Day
median (full range (min-max))
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 3, 0, 0, 0, 0)	0.87 (0.87 to 0.87)	1.49 (1.49 to 1.49)	1.362 (1.02 to 1.39)	1.384 (1.19 to 1.65)	2.004 (1.67 to 2.53)	1.810 (1.53 to 2.74)	2.153 (1.99 to 2.60)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1.097 (0.66 to 1.56)	1.398 (0.91 to 1.81)	1.423 (0.77 to 1.96)	2.05 (2.05 to 2.05)
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0, 0, 0, 0, 0)	0.78 (0.78 to 0.78)	1.07 (1.07 to 1.07)	1.130 (1.13 to 1.13)	1.68 (1.68 to 1.68)	2.117 (1.55 to 2.90)	2.035 (1.38 to 2.74)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	1.51 (1.51 to 1.51)	1.44 (1.44 to 1.44)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Volume of Distribution at Steady State (Vss) of Conjugated Enapotamab Vedotin for Dose-escalation Part

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End point title

Volume of Distribution at Steady State (Vss) of Conjugated Enapotamab Vedotin for Dose-escalation Part ^[16]

End point description

The Vss of conjugated enapotamab vedotin for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: L/day
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 3, 0, 0, 0, 0)	4.909 ( 99999.0 )	6.544 ( 99999.0 )	5.873 ( 9.8 )	4.208 ( 12.5 )	6.028 ( 18.4 )	5.489 ( 24.2 )	5.038 ( 27.3 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	57.736 ( 10.0 )	48.001 ( 91.1 )	53.436 ( 28.0 )	42.708 ( 99999.0 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 0, 0, 0, 0, 0)	4.755 ( 99999.0 )	6.288 ( 99999.0 )	4.870 ( 99999.0 )	4.534 ( 99999.0 )	6.072 ( 24.2 )	6.656 ( 22.0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	36.476 ( 99999.0 )	53.085 ( 99999.0 )	0 ( 0 )

No statistical analyses for this end point

Secondary: AUC0-inf of Free Toxin Monomethyl Auristatin E (MMAE) for Dose-escalation Part

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End point title

AUC0-inf of Free Toxin Monomethyl Auristatin E (MMAE) for Dose-escalation Part ^[17]

End point description

The AUC0-inf of MMAE for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3
Units: Day*pg/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n = 1, 1, 3, 3, 10, 10, 2)	3832.48 ( 99999 )	6144.11 ( 99999 )	13673.7 ( 110.4 )	26549.1 ( 82.9 )	33494.5 ( 47.1 )	50459.6 ( 117.0 )	48626.4 ( 95.5 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1)	3248.46 ( 99999 )	7452.05 ( 99999 )	4338.20 ( 99999 )	47093.9 ( 99999 )	30512.0 ( 47.8 )	34188.6 ( 46.6 )	16754.5 ( 99999 )

No statistical analyses for this end point

Secondary: AUC0-last of MMAE for Dose-escalation Part

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End point title

AUC0-last of MMAE for Dose-escalation Part ^[18]

End point description

The AUC0-last of MMAE for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3
Units: day*pg/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n = 1, 1, 3, 3, 10, 10, 3)	3364.64 ( 99999.0 )	5980.86 ( 99999.0 )	13194.4 ( 110.4 )	25549.3 ( 80.8 )	31854.7 ( 46.4 )	34659.4 ( 81.2 )	38963.5 ( 65.4 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1)	2642.23 ( 99999.0 )	7263.16 ( 99999.0 )	4156.66 ( 99999.0 )	44553.3 ( 99999.0 )	28890.0 ( 47.4 )	31429.9 ( 43.2 )	16354.3 ( 99999.0 )

No statistical analyses for this end point

Secondary: Cmax of MMAE for Dose-escalation Part

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End point title

Cmax of MMAE for Dose-escalation Part ^[19]

End point description

The Cmax of MMAE for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: pg/mL
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 3, 3, 3, 6, 3)	700.000 ( 99999.0 )	947.000 ( 99999.0 )	1847.13 ( 149.5 )	4036.47 ( 81.8 )	4265.60 ( 46.1 )	5154.48 ( 61.9 )	5617.89 ( 34.7 )	161.140 ( 75.0 )	175.315 ( 159.4 )	303.977 ( 45.3 )	244.623 ( 48.9 )
Cycle1 Day8 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 3)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	738.227 ( 28.2 )	766.467 ( 91.4 )	1982.67 ( 58.1 )	1553.93 ( 86.2 )
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	1715.54 ( 42.8 )	2525.75 ( 54.7 )	4379.50 ( 58.2 )	3720.00 ( 99999.0 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1, 0, 1, 1, 0)	631.000 ( 99999.0 )	1200.00 ( 99999.0 )	628.000 ( 99999.0 )	6500.00 ( 99999.0 )	3964.40 ( 49.4 )	4127.31 ( 39.3 )	2180.00 ( 99999.0 )	0 ( 0 )	442.000 ( 99999.0 )	558.000 ( 99999.0 )	0 ( 0 )
Cycle3 Day8 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 0, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	1060.00 ( 99999.0 )	0 ( 0 )	0 ( 0 )
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	2960.00 ( 99999.0 )	5190.00 ( 99999.0 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Total CL of MMAE in Dose-escalation Part

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End point title

Total CL of MMAE in Dose-escalation Part ^[20]

End point description

The total CL of MMAE in dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point. The arbitrary number ‘99999.0’ denotes the data for geometric coefficient of variation, which was not determined because an insufficient number of participants was evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: L/day
geometric mean (geometric coefficient of variation)
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 2, 0, 0, 0, 0)	6497.09 ( 99999.0 )	7421.74 ( 99999.0 )	4748.64 ( 87.2 )	3555.78 ( 90.6 )	4216.71 ( 42.0 )	2971.09 ( 107.2 )	2813.05 ( 35.9 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	4819.44 ( 25.8 )	4666.23 ( 35.5 )	2847.55 ( 46.7 )	0 ( 0 )
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1, 0, 0, 0, 0)	7757.51 ( 99999.0 )	6119.12 ( 99999.0 )	12908.6 ( 99999.0 )	1815.52 ( 99999.0 )	4256.44 ( 50.1 )	4542.22 ( 42.8 )	5849.18 ( 99999.0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	0 ( 0 )	3899.39 ( 99999.0 )	2507.90 ( 99999.0 )	0 ( 0 )

No statistical analyses for this end point

Secondary: Tmax of MMAE for Dose-escalation Part

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End point title

Tmax of MMAE for Dose-escalation Part ^[21]

End point description

The Tmax of MMAE for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: Day
median (full range (min-max))
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 3, 0, 0, 0, 0)	2.95 (2.95 to 2.95)	3.00 (3.00 to 3.00)	2.938 (2.89 to 2.94)	2.764 (2.72 to 2.83)	2.852 (0.97 to 3.03)	2.866 (1.00 to 6.85)	2.942 (2.82 to 7.00)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 1)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	15.950 (15.93 to 17.73)	15.982 (15.97 to 15.99)	15.911 (14.51 to 15.95)	20.820 (20.82 to 20.82)
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1, 0, 0, 0, 0)	2.83 (2.83 to 2.83)	2.87 (2.87 to 2.87)	0.94 (0.94 to 0.94)	2.83 (2.83 to 2.83)	2.830 (0.94 to 3.96)	2.727 (0.94 to 2.94)	3.02 (3.02 to 3.02)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	14.93 (14.93 to 14.93)	15.890 (15.89 to 15.89)	0 (0 to 0)

No statistical analyses for this end point

Secondary: t1/2 of MMAE for Dose-escalation Part

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End point title

t1/2 of MMAE for Dose-escalation Part ^[22]

End point description

The t1/2 of MMAE for dose-escalation part is reported. The PK analysis set was analysed which included all participants who were exposed to at least 1 dose of enapotamab vedotin and who had at least 1 postdose PK measurement. Here ‘n’ denotes the number of participants evaluated for the specified time point.

End point type

Secondary

End point timeframe

For 1Q3W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 1 of Cycles 1 and 3; For 3Q4W dosing regimen: Predose, EOI, and 2 and 5 hours after EOI on Day 15 of Cycles 1 and 3

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3
Units: Day
median (full range (min-max))
Cycle1 Day1 (n= 1, 1, 3, 3, 10, 10, 2, 0, 0, 0, 0)	2.19 (2.19 to 2.19)	2.35 (2.35 to 2.35)	2.470 (2.10 to 2.70)	2.620 (1.85 to 2.98)	2.420 (2.02 to 3.75)	3.128 (1.55 to 42.73)	2.835 (2.45 to 3.22)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)
Cycle1 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 3, 3, 6, 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	3.976 (2.78 to 6.06)	3.115 (2.49 to 5.04)	4.739 (2.85 to 8.70)	0 (0 to 0)
Cycle3 Day1 (n = 1, 1, 1, 1, 8, 4, 1, 0, 0, 0, 0)	1.94 (1.94 to 1.94)	2.32 (2.32 to 2.32)	2.71 (2.71 to 2.71)	2.52 (2.52 to 2.52)	2.746 (2.18 to 3.12)	3.364 (2.85 to 4.99)	1.98 (1.98 to 1.98)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 00)
Cycle3 Day15 (n = 0, 0, 0, 0, 0, 0, 0, 0, 1, 1, 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	0 (0 to 0)	2.330 (2.33 to 2.33)	3.37 (3.37 to 3.37)	0 (0 to 0)

No statistical analyses for this end point

Secondary: Number of Participants With Antidrug Antibodies (ADAs) Confirmed Positive to Enapotamab Vedotin

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End point title

Number of Participants With Antidrug Antibodies (ADAs) Confirmed Positive to Enapotamab Vedotin ^[23]

End point description

The ADA assessment was performed according to a tiered approach. First samples were screened for an ADA response; positively screened samples were analysed in a confirmation method. Subsequently confirmed positive samples were analysed for titre and the presence of neutralizing antibodies. The number of participants with ADA confirmed positive to enapotamab vedotin is reported. The safety set was analysed which included all participants who received at least 1 dose of enapotamab vedotin, had at least one valid post-baseline safety assessment, and were classified according to first dose received.

End point type

Secondary

End point timeframe

Day 1 through Day 1130 (Dose-escalation part: Predose of Day 1 of Cycles 1 to 12, end of treatment [EOT], and 30 days after last study drug; Expansion part: Predose on Day 1 of Cycles 1 to 5, then every fourth cycle until PD)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	26	56	20
Units: Participants	0	0	1	1	5	1	1	0	0	2	0	0	4	1	3	0	7	0	5	0

No statistical analyses for this end point

Secondary: Number of Participants With Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) As Assessed by Investigator

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End point title

Number of Participants With Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) As Assessed by Investigator

End point description

Radiological evaluation based on RECIST v1.1 was performed by the investigator using computed tomography (CT) scans/ magnetic resonance imaging (MRI) scans/ positron emission tomography (PET) scans. The OR was defined as confirmed CR or confirmed PR per RECIST v1.1. The changes in tumor measurements that were confirmed by repeat assessments performed no less than 4 weeks after initial response are called confirmed responses. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to < 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions taking as reference the baseline sum of LD. The full analysis set was analysed which included all participants who received at least 1 dose of enapotamab vedotin and were analysed according to the assigned treatment/dose (planned dose level and schedule).

End point type

Secondary

End point timeframe

Day 1 through 44.5 months (maximum observed duration)

End point values	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W
Number of subjects analysed	1	1	3	3	10	11	3	3	3	6	3	22	16	25	25	44	25	55	21	26
Units: Participants	0	0	0	1	0	1	1	0	0	0	0	1	2	3	0	4	2	5	1	3

No statistical analyses for this end point

Secondary: Number of Participants With Best Cancer Antigen 125 (CA-125) Response

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End point title

Number of Participants With Best Cancer Antigen 125 (CA-125) Response ^[24]

End point description

The best CA-125 response was evaluated in participants with ovarian cancer. A CA-125 partial response was defined as at least a 50% reduction in CA-125 levels in blood from a pretreatment sample. Participants who had a CA-125 partial response and had CA-125 level falls to within the reference range (0-35 units/mL) were classified as CA-125 complete responders. The response was confirmed and maintained for at least 28 days. The best overall response (CA-125 partial response and CA-125 complete response) is reported. Participants from the full analysis set with ovarian cancer who had an initial CA-125 level of at least twice the upper limit of the reference range within 2 weeks before starting the study treatment were evaluated for this end point.

End point type

Secondary

End point timeframe

From Screening (within 2 weeks before starting of the study treatment) through Day 1130 (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W
Number of subjects analysed	1	1	3	3	1	1	2	2	19
Units: Participants
CA-125 partial response	0	0	0	0	1	0	0	0	2
CA-125 complete response	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Duration of Response (DoR) Based on RECIST v1.1 as Assessed by Investigator for Expansion Part

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End point title

Duration of Response (DoR) Based on RECIST v1.1 as Assessed by Investigator for Expansion Part ^[25]

End point description

The DoR was defined as number of months from first documentation of OR (confirmed CR or confirmed PR) to the date of first progressive disease (PD) or death. The OR was defined in the earlier end point. The PD was defined as at least 20% increase in the sum of LD of target lesions taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of one or more new target and non-target lesions and/or unequivocal progression of existing non-target lesions. Participants from the full analysis set who achieved confirmed OR by the investigator assessment were evaluated for this end point. Here, the arbitrary number ‘999.0’ denotes the data for median and ‘0.9999’ and ‘9999.9’ denote the lower and upper limits of confidence interval, respectively, which were not determined because an insufficient number of participants was evaluated.

End point type

Secondary

End point timeframe

Day 1 through 44.5 months (maximum observed duration)

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: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W
Number of subjects analysed	0 ^[26]	1	2	0 ^[27]	2	1	1	1	1
Units: Months
median (confidence interval 95%)	( to )	4.2 (0.9999 to 9999.9)	4.1 (2.4 to 9999.9)	( to )	4.9 (2.6 to 9999.9)	3.0 (0.9999 to 9999.9)	999.0 (3.0 to 9999.9)	3.0 (0.9999 to 9999.9)	4.9 (0.9999 to 9999.9)

Notes
[26] - No participants with confirmed OR by the investigator assessment.
[27] - No participants with confirmed OR by the investigator assessment.

No statistical analyses for this end point

Secondary: Progression Free Survival (PFS) as Assessed by Investigator

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End point title

Progression Free Survival (PFS) as Assessed by Investigator

End point description

The PFS was defined as the number of months from the date of first study drug administration to first PD or death. The PD was defined as at least 20% increase in the sum of longest diameters of target lesions taking as reference the smallest sum of the longest diameters recorded since the treatment started or the appearance of one or more new lesions. The PFS was estimated using Kaplan-Meier method. The full analysis set was analysed which included all participants who received at least 1 dose of enapotamab vedotin and were analysed according to the assigned treatment/dose (planned dose level and schedule). Here, the arbitrary numbers ‘0.9999’ and ‘9999.9’ denote the lower and upper limits of confidence interval, respectively and ‘999.0’ denotes the data for median, which were not determined because an insufficient number of participants was evaluated.

End point type

Secondary

End point timeframe

Day 1 through 44.5 months (maximum observed duration)

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Number of subjects analysed

Units: Months

median (confidence interval 95%)

6.7 (0.9999 to 9999.9)

3.5 (0.9999 to 9999.9)

1.3 (1.2 to 9999.9)

5.3 (1.1 to 9999.9)

2.8 (1.4 to 9999.9)

2.6 (0.7 to 9999.9)

999.0 (0.9999 to 9999.9)

1.6 (0.9999 to 9999.9)

1.6 (1.3 to 9999.9)

4.3 (1.0 to 9999.9)

0.8 (0.4 to 9999.9)

2.6 (1.2 to 2.8)

2.6 (1.2 to 3.9)

2.8 (1.3 to 5.0)

2.6 (1.4 to 4.1)

1.9 (1.6 to 2.1)

1.6 (1.3 to 3.0)

2.2 (1.4 to 3.9)

2.6 (1.1 to 4.0)

2.0 (1.4 to 4.1)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

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End point title

Overall Survival (OS)

End point description

Overall survival was defined as the number of months from date of first study drug administration to death. The OS was estimated using Kaplan-Meier method. The full analysis set was analysed which included all participants who received at least 1 dose of enapotamab vedotin and were analysed according to the assigned treatment/dose (planned dose level and schedule). Here, the arbitrary numbers ‘0.9999’ and ‘9999.9’ denote the lower and upper limits of confidence interval, respectively and ‘999.0’ denotes the data for median, which were not determined because an insufficient number of participants was evaluated.

End point type

Secondary

End point timeframe

Day 1 through 44.5 months (maximum observed duration)

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Number of subjects analysed

Units: Months

median (confidence interval 95%)

999.0 (0.9999 to 9999.9)

4.3 (0.9999 to 9999.9)

6.4 (6.3 to 9999.9)

999.0 (6.7 to 9999.9)

14.5 (3.1 to 9999.9)

7.6 (2.2 to 12.1)

44.5 (0.9999 to 9999.9)

6.7 (6.7 to 9999.9)

14.3 (0.9999 to 9999.9)

7.7 (4.3 to 9999.9)

21.7 (0.4 to 9999.9)

16.5 (4.1 to 25.9)

8.6 (3.6 to 19.1)

9.2 (4.0 to 14.9)

17.1 (5.7 to 24.3)

7.0 (5.2 to 11.6)

8.4 (6.5 to 12.4)

11.3 (8.0 to 15.5)

8.7 (5.8 to 14.1)

8.0 (4.1 to 12.9)

No statistical analyses for this end point

Secondary: Change in AXL Expression (Total Tumor H-score) From Baseline to EOT Visit for Expansion Part

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End point title

Change in AXL Expression (Total Tumor H-score) From Baseline to EOT Visit for Expansion Part ^[28]

End point description

Change in AXL expression (total humor H-score in membrane or cytoplasm) from baseline to EOT visit for the expansion part is reported. The H-score captures both the intensity and proportion of AXL positive tumor cells and was defined by the formula: H-score = (1 × % 1+ tumor cells) + (2 × % 2+ tumor cells) + (3 × % 3+ tumor cells); where '1+' indicates weak staining intensity, '2+' indicates medium staining intensity, and '3+' indicates strong staining intensity. The H-score values ranges from 0 to 300. Lower H-scores represent lower AXL expression in the tumor sample, while higher scores represent stronger AXL expression in the tumor samples. Participants from the full analysis set who had tumor H-scores in membrane/cytoplasm assessed at Baseline and at the EOT visit were evaluated. The arbitrary number ‘99999.9’ denotes data for standard deviation, which was not determined because an insufficient participants was evaluated.

End point type

Secondary

End point timeframe

Baseline (Study Days -21 to 1) and EOT visit (Day 1100)

Notes
[28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only those baseline period arms for which analysis was planned were reported in the end point.

End point values	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W
Number of subjects analysed	1	1	0 ^[29]	1	0 ^[30]	1	1	0 ^[31]	0 ^[32]
Units: Scores on a scale
arithmetic mean (standard error)	-8.0 ( 99999.9 )	-1.0 ( 99999.9 )	( )	-30.0 ( 99999.9 )	( )	35.0 ( 99999.9 )	-14.0 ( 99999.9 )	( )	( )

Notes
[29] - No participant had tumor H-score in membrane/cytoplasm at Baseline and EOT visit.
[30] - No participant had tumor H-score in membrane/cytoplasm at Baseline and EOT visit.
[31] - No participant had tumor H-score in membrane/cytoplasm at Baseline and EOT visit.
[32] - No participant had tumor H-score in membrane/cytoplasm at Baseline and EOT visit.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

For TEAEs: Day 1 through Day 1130 and for all-cause mortality: From date of inform consent form until death (up to 44.5 months) (maximum observed duration)

Adverse event reporting additional description

The TEAEs were evaluated per the safety set and all-cause mortality was evaluated per the full analysis set.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

v24.0

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.3 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.5 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.0 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 2.4 mg/kg 1Q3W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.6 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 0.8 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Reporting group title

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Reporting group description

Participants with relapsed/refractory cancer (ovarian, cervical, endometrial, thyroid, NSCLC, or melanoma) received IV infusion of enapotamab vedotin 1.2 mg/kg 3Q4W until the end of treatment.

Reporting group title

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic NSCLC with classical sensitizing EGFR mutations and/or EGFR mutations targeted by third-generation tyrosine kinase inhibitors) received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 mutation received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic melanoma with BRAF V600 wild type received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic sarcoma received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Reporting group title

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic platinum-resistant ovarian cancer received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.0 mg/kg 3Q4W until the end of treatment.

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 2.2 mg/kg 1Q3W until the end of treatment.

Reporting group title

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Reporting group description

Participants with advanced and/or metastatic NSCLC without activating EGFR mutations or ALK rearrangements received IV infusion of enapotamab vedotin 1.8 mg/kg 1Q3W until the end of treatment.

Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W

Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W

Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W

Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W

Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

2 / 3 (66.67%)

7 / 10 (70.00%)

6 / 11 (54.55%)

2 / 3 (66.67%)

1 / 3 (33.33%)

0 / 3 (0.00%)

2 / 6 (33.33%)

3 / 3 (100.00%)

15 / 22 (68.18%)

5 / 16 (31.25%)

16 / 25 (64.00%)

10 / 25 (40.00%)

16 / 44 (36.36%)

12 / 25 (48.00%)

14 / 26 (53.85%)

33 / 56 (58.93%)

7 / 20 (35.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Lymphangiosis Carcinomatosa

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

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 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

2 / 11 (18.18%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

4 / 25 (16.00%)

0 / 25 (0.00%)

2 / 44 (4.55%)

0 / 25 (0.00%)

1 / 26 (3.85%)

3 / 56 (5.36%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 4

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

0 / 0

Metastases To Central Nervous System

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Metastases to Peritoneum

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neoplasm Progression

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (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

Pericardial Effusion Malignant

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Deep Vein Thrombosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Embolism

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peripheral Embolism

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Chest Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Death

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (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

Fatigue

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

General Physical Health Deterioration

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

3 / 25 (12.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Influenza Like Illness

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Multiple Organ Dysfunction Syndrome

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (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

Non-Cardiac Chest Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oedema

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (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 / 1 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

2 / 25 (8.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute Respiratory Failure

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (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

Dysphonia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

2 / 26 (7.69%)

3 / 56 (5.36%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 3

1 / 1

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Hypoxia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (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

Pneumonia Aspiration

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (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

Pneumonitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (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 Embolism

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

3 / 22 (13.64%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

1 / 26 (3.85%)

4 / 56 (7.14%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

1 / 3

0 / 0

0 / 1

0 / 4

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Tracheal Obstruction Extrinsic

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional State

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Delirium

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (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 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychotic Disorder

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Product issues

Device Occlusion

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Blood Creatine Phosphokinase Increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood Creatinine Increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lipase Increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Lymphocyte Count Decreased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutrophil Count Decreased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

White Blood Cell Count Decreased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Femoral Neck Fracture

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hip Fracture

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial Fibrillation

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac Tamponade

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Supraventricular Tachycardia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (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

Nervous system disorders

Acute Motor-Sensory Axonal Neuropathy

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular Accident

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalopathy

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Loss of Consciousness

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Monoplegia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neuralgia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Partial Seizures

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peripheral Motor Neuropathy

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peripheral Sensorimotor Neuropathy

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 11 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

2 / 25 (8.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Somnolence

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Transient Ischaemic Attack

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

1 / 6 (16.67%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile Neutropenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

1 / 44 (2.27%)

1 / 25 (4.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

2 / 25 (8.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal Pain Upper

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Colitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

3 / 56 (5.36%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

4 / 10 (40.00%)

1 / 11 (9.09%)

2 / 3 (66.67%)

1 / 3 (33.33%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

7 / 22 (31.82%)

4 / 16 (25.00%)

4 / 25 (16.00%)

3 / 25 (12.00%)

2 / 44 (4.55%)

0 / 25 (0.00%)

1 / 26 (3.85%)

3 / 56 (5.36%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

4 / 4

1 / 1

2 / 2

1 / 1

0 / 0

1 / 1

0 / 0

7 / 7

4 / 4

3 / 3

2 / 2

0 / 0

1 / 1

4 / 4

1 / 1

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

1 / 1

0 / 0

1 / 1

0 / 1

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (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 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal Obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

1 / 25 (4.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 22 (4.55%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

4 / 56 (7.14%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 6

1 / 1

deaths causally related to treatment / all

0 / 0

Pancreatitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small Intestinal Obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

2 / 25 (8.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

1 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

2 / 22 (9.09%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

1 / 25 (4.00%)

0 / 26 (0.00%)

3 / 56 (5.36%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

0 / 1

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary Obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

1 / 25 (4.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Drug-Induced Liver Injury

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

1 / 26 (3.85%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Portal Vein Thrombosis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Adrenal Insufficiency

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Inappropriate Antidiuretic Hormone Secretion

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 11 (9.09%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (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

Bone Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Flank Pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Myalgia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

1 / 16 (6.25%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

1 / 20 (5.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (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

Bronchitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 25 (4.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cholangitis Infective

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (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 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower Respiratory Tract Infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenic Sepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumocystis Jirovecii Infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

1 / 44 (2.27%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

4 / 22 (18.18%)

0 / 16 (0.00%)

0 / 25 (0.00%)

2 / 44 (4.55%)

1 / 25 (4.00%)

1 / 26 (3.85%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 2

0 / 1

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

Sepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

Septic Shock

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

2 / 25 (8.00%)

1 / 26 (3.85%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 1

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 1

1 / 1

0 / 0

Staphylococcal Bacteraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary Tract Infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

1 / 25 (4.00%)

0 / 25 (0.00%)

2 / 44 (4.55%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Dehydration

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

2 / 56 (3.57%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

2 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

0 / 56 (0.00%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypocalcaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 22 (0.00%)

1 / 16 (6.25%)

1 / 25 (4.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

3 / 56 (5.36%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 1

0 / 0

2 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Hypophosphataemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 11 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 22 (0.00%)

0 / 16 (0.00%)

0 / 25 (0.00%)

0 / 44 (0.00%)

0 / 25 (0.00%)

0 / 26 (0.00%)

1 / 56 (1.79%)

0 / 20 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Dose-escalation Part: Enapotamab Vedotin 0.3 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 1.5 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.0 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 2.4 mg/kg 1Q3W	Dose-escalation Part: Enapotamab Vedotin 0.6 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 0.8 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Dose-escalation Part: Enapotamab Vedotin 1.2 mg/kg 3Q4W	Expansion Part Cohort 1: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 3: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 4: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 5: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 6: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 7: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 8: Enapotamab Vedotin 1.0 mg/kg 3Q4W	Expansion Part Cohort 2: Enapotamab Vedotin 2.2 mg/kg 1Q3W	Expansion Part Cohort 2: Enapotamab Vedotin 1.8 mg/kg 1Q3W
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 1 (100.00%)	1 / 1 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	10 / 10 (100.00%)	11 / 11 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	22 / 22 (100.00%)	16 / 16 (100.00%)	24 / 25 (96.00%)	25 / 25 (100.00%)	44 / 44 (100.00%)	25 / 25 (100.00%)	23 / 26 (88.46%)	56 / 56 (100.00%)	20 / 20 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	3
Vascular disorders
Deep Vein Thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Flushing
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hot Flush
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	2	0	1	0	0	0	0	0	0	0	1	1	2	0	0	0	0
Hypertension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 3 (0.00%)	3 / 22 (13.64%)	4 / 16 (25.00%)	1 / 25 (4.00%)	3 / 25 (12.00%)	0 / 44 (0.00%)	4 / 25 (16.00%)	1 / 26 (3.85%)	3 / 56 (5.36%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	1	1	0	0	1	1	0	3	4	1	9	0	4	1	3	0
Hypotension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	3 / 25 (12.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	7 / 56 (12.50%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	2	3	1	0	1	7	0
Jugular Vein Thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Orthostatic Hypotension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	1	0	2	1	0
Thrombophlebitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Thrombophlebitis Superficial
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vascular Compression
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
General disorders and administration site conditions
Application Site Reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Asthenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	2 / 26 (7.69%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	0	1	0	0	1	0	0	1	0	0	0	1	1	2	3	1
Axillary Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Chest Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Chest Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	4 / 25 (16.00%)	2 / 26 (7.69%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	1	0	3	5	2	3	1
Chills
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	2 / 25 (8.00%)	2 / 25 (8.00%)	4 / 44 (9.09%)	2 / 25 (8.00%)	5 / 26 (19.23%)	3 / 56 (5.36%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	1	0	1	2	2	5	4	2	5	3	2
Condition Aggravated
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Face Oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Fatigue
subjects affected / exposed	1 / 1 (100.00%)	1 / 1 (100.00%)	2 / 3 (66.67%)	3 / 3 (100.00%)	5 / 10 (50.00%)	8 / 11 (72.73%)	3 / 3 (100.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	5 / 6 (83.33%)	2 / 3 (66.67%)	13 / 22 (59.09%)	8 / 16 (50.00%)	16 / 25 (64.00%)	14 / 25 (56.00%)	23 / 44 (52.27%)	13 / 25 (52.00%)	13 / 26 (50.00%)	31 / 56 (55.36%)	11 / 20 (55.00%)
occurrences all number	1	1	3	3	5	10	3	1	2	14	3	15	9	22	22	31	17	14	37	13
Feeling Abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0
Gait Disturbance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	1	0	0	0	1	0	0	2
Hernia Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Influenza Like Illness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	2	2
Infusion Site Reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Localised Oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Malaise
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	2 / 25 (8.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	2	1	0	0
Medical Device Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Mucosal Inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Nodule
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Non-cardiac Chest Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	2	0	2	1	0
Oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	0	0
Oedema Peripheral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	2 / 25 (8.00%)	1 / 25 (4.00%)	3 / 44 (6.82%)	2 / 25 (8.00%)	1 / 26 (3.85%)	2 / 56 (3.57%)	4 / 20 (20.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	1	0	2	0	3	3	3	2	1	3	6
Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	1 / 25 (4.00%)	3 / 44 (6.82%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	2	3	0	0	0	1
Peripheral Swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Physical Deconditioning
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Pyrexia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 10 (20.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	5 / 22 (22.73%)	3 / 16 (18.75%)	5 / 25 (20.00%)	0 / 25 (0.00%)	5 / 44 (11.36%)	1 / 25 (4.00%)	2 / 26 (7.69%)	7 / 56 (12.50%)	3 / 20 (15.00%)
occurrences all number	0	0	1	3	2	0	1	1	0	2	0	6	4	6	0	6	2	3	7	4
Soft Tissue Inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Temperature Intolerance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Tenderness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vaccination Site Reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Xerosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Reproductive system and breast disorders
Benign Prostatic Hyperplasia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Breast Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	2 / 25 (8.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Dysmenorrhoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Perineal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vaginal Discharge
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Vaginal Haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	2	0	0	0	0	0	0	1	0	0	0	0
Vulvovaginal Dryness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1
Vulvovaginal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Respiratory, thoracic and mediastinal disorders
Adductor Vocal Cord Weakness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Aspiration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Cough
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	4 / 25 (16.00%)	3 / 25 (12.00%)	5 / 44 (11.36%)	2 / 25 (8.00%)	3 / 26 (11.54%)	5 / 56 (8.93%)	2 / 20 (10.00%)
occurrences all number	0	1	1	0	1	1	4	0	1	0	0	1	0	4	3	6	2	10	5	3
Dysaesthesia Pharynx
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Dysphonia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	1 / 16 (6.25%)	3 / 25 (12.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	2	1	3	1	1	1	0	1	0
Dyspnoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	3 / 11 (27.27%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	5 / 22 (22.73%)	0 / 16 (0.00%)	4 / 25 (16.00%)	2 / 25 (8.00%)	4 / 44 (9.09%)	2 / 25 (8.00%)	10 / 26 (38.46%)	6 / 56 (10.71%)	6 / 20 (30.00%)
occurrences all number	0	0	0	1	0	3	2	0	0	0	0	5	0	4	2	4	3	12	8	7
Dyspnoea Exertional
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	2 / 25 (8.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	1	2	0	1	0
Epistaxis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	2	1	0
Hypoventilation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hypoxia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Nasal Congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	1
Nasal Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Oropharyngeal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	2 / 25 (8.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	2 / 26 (7.69%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	0	2	0	0	3	2	0
Paranasal Sinus Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Pleural Effusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	2 / 56 (3.57%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	1	2	1
Pleuritic Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	2 / 26 (7.69%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0
Pneumonia Aspiration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Pneumonitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	1
Productive Cough
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	0	3	1
Pulmonary Embolism
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	1 / 25 (4.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	1	1	1
Pulmonary Haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Rhinitis Allergic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Rhinorrhoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	2 / 26 (7.69%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0
Sinus Congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Sinus Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Sinus Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Upper-airway Cough Syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vasomotor Rhinitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Wheezing
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	2	0	0
Psychiatric disorders
Agitation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Anxiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	2 / 25 (8.00%)	1 / 25 (4.00%)	3 / 44 (6.82%)	1 / 25 (4.00%)	1 / 26 (3.85%)	3 / 56 (5.36%)	2 / 20 (10.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	2	0	2	1	3	1	1	3	2
Confusional State
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	0	2	1
Delirium
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Depressed Mood
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Depression
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	2 / 16 (12.50%)	1 / 25 (4.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	1	1	2	0	2	1	0
Hallucination
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hallucination, Olfactory
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Hallucination, Visual
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Insomnia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	2 / 25 (8.00%)	5 / 44 (11.36%)	5 / 25 (20.00%)	7 / 26 (26.92%)	8 / 56 (14.29%)	3 / 20 (15.00%)
occurrences all number	0	0	0	1	1	2	0	0	0	0	0	0	0	3	3	5	5	7	8	3
Irritability
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Mental Status Changes
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Restlessness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Investigations
Activated Partial Thromboplastin Time Prolonged
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
Alanine Aminotransferase Increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	4 / 11 (36.36%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 3 (33.33%)	6 / 22 (27.27%)	3 / 16 (18.75%)	4 / 25 (16.00%)	6 / 25 (24.00%)	3 / 44 (6.82%)	5 / 25 (20.00%)	2 / 26 (7.69%)	10 / 56 (17.86%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	1	5	3	0	2	0	1	6	4	6	9	3	6	2	11	0
Amylase Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	3 / 22 (13.64%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	3 / 25 (12.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	3	0	0	0	0	0	0	3	0	1	0	2	4	0	6	2
Aspartate Aminotransferase Increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	3 / 10 (30.00%)	3 / 11 (27.27%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 3 (33.33%)	6 / 22 (27.27%)	2 / 16 (12.50%)	3 / 25 (12.00%)	6 / 25 (24.00%)	3 / 44 (6.82%)	6 / 25 (24.00%)	1 / 26 (3.85%)	13 / 56 (23.21%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	9	4	4	0	2	2	1	6	2	4	10	3	7	1	17	0
Blood Albumin Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	4 / 22 (18.18%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	2 / 26 (7.69%)	6 / 56 (10.71%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	1	2	0	0	0	0	1	4	0	2	0	0	1	2	6	0
Blood Bilirubin Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	4	0	0	1	0
Blood Cholesterol Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	1
Blood Creatine Phosphokinase Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	3	0
Blood Creatinine Increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	0	5	0	1	0	0	0	1	1	1	2	0
Blood Iron Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood Lactate Dehydrogenase Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Blood Magnesium Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood Phosphorus Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Blood Potassium Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Blood Sodium Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood Thyroid Stimulating Hormone Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood Triglycerides Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	1	0
Blood Urea Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Brain Natriuretic Peptide Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Breath Sounds Abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
C-reactive Protein Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	6	0
Electrocardiogram QT Prolonged
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Gamma-glutamyltransferase Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	3 / 11 (27.27%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	2 / 22 (9.09%)	0 / 16 (0.00%)	2 / 25 (8.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	6 / 25 (24.00%)	3 / 26 (11.54%)	3 / 56 (5.36%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	2	4	2	0	0	1	1	2	0	2	1	1	6	3	3	0
Glomerular Filtration Rate Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
International Normalised Ratio Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	4	0	0	1	0
Lipase Increased
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	4 / 22 (18.18%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	2 / 25 (8.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	1	0	5	0	1	1	2	2	0	4	1
Lymphocyte Count Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	2 / 25 (8.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	4	3	0	0	0
Neutrophil Count Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	2	0
Platelet Count Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
SARS-CoV-2 Test Positive
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Staphylococcus Test Positive
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Troponin T Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Troponin Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vitamin B12 Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Weight Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	4 / 11 (36.36%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	5 / 22 (22.73%)	1 / 16 (6.25%)	3 / 25 (12.00%)	3 / 25 (12.00%)	8 / 44 (18.18%)	0 / 25 (0.00%)	5 / 26 (19.23%)	13 / 56 (23.21%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	2	4	0	0	0	2	0	5	1	3	3	8	0	5	13	2
Weight Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
White Blood Cell Count Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1	0	3	1	2	0	0
White Blood Cells Urine Positive
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Clavicle Fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Compression Fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Contusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Fall
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	2 / 25 (8.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	1	2	1	0	0	1	0	0
Infusion Related Reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	2 / 25 (8.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0
Injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Ligament Sprain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Lip Injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Lumbar Vertebral Fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Overdose
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Post Procedural Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Post Procedural Swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Procedural Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	3	0
Radiation Necrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Tendon Rupture
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Thermal Burn
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Wound
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Wrist Fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Cardiac disorders
Atrial Fibrillation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Palpitations
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Pericardial Effusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Sinus Tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	0	0	0	1	0	0	0	0	0	0	0	0
Supraventricular Tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	2 / 25 (8.00%)	3 / 25 (12.00%)	3 / 44 (6.82%)	1 / 25 (4.00%)	2 / 26 (7.69%)	4 / 56 (7.14%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	1	2	4	3	1	2	4	0
Ventricular Extrasystoles
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Nervous system disorders
Amputation Stump Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Autonomic Nervous System Imbalance
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Autonomic Neuropathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Balance Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Carpal Tunnel Syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	0	0
Cognitive Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Depressed Level of Consciousness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Disturbance in Attention
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Dizziness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	3 / 16 (18.75%)	0 / 25 (0.00%)	0 / 25 (0.00%)	3 / 44 (6.82%)	0 / 25 (0.00%)	4 / 26 (15.38%)	5 / 56 (8.93%)	3 / 20 (15.00%)
occurrences all number	0	0	1	0	1	1	1	0	0	0	0	2	3	0	0	4	0	5	5	3
Dysaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Dysgeusia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 11 (27.27%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	1 / 25 (4.00%)	5 / 25 (20.00%)	6 / 44 (13.64%)	0 / 25 (0.00%)	5 / 26 (19.23%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	1	1	1	5	7	0	5	2	0
Headache
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	3 / 11 (27.27%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	2 / 25 (8.00%)	4 / 25 (16.00%)	5 / 44 (11.36%)	5 / 25 (20.00%)	4 / 26 (15.38%)	5 / 56 (8.93%)	4 / 20 (20.00%)
occurrences all number	1	0	0	0	1	4	0	0	0	0	0	2	0	2	5	11	6	10	7	4
Hyperaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hypoaesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	1	0
Lethargy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	1 / 25 (4.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	2	0	1	0
Metabolic Encephalopathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Migraine
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Mononeuropathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Monoplegia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Neuralgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	2 / 25 (8.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	0	0	0	3	0	0	0	0	0
Neuropathy Peripheral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	5 / 44 (11.36%)	0 / 25 (0.00%)	3 / 26 (11.54%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	6	0	3	1	1
Neurotoxicity
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Paraesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	1 / 16 (6.25%)	1 / 25 (4.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	2	1	2	1	3	0	1	1	0
Paresis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Parosmia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Peripheral Motor Neuropathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	4 / 56 (7.14%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	1	0	0	1	1	0	4	0
Peripheral Sensorimotor Neuropathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	3 / 25 (12.00%)	1 / 25 (4.00%)	3 / 44 (6.82%)	1 / 25 (4.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	1	5	1	3	1	0	2	0
Peripheral Sensory Neuropathy
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	5 / 10 (50.00%)	2 / 11 (18.18%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	9 / 22 (40.91%)	2 / 16 (12.50%)	4 / 25 (16.00%)	7 / 25 (28.00%)	11 / 44 (25.00%)	6 / 25 (24.00%)	7 / 26 (26.92%)	11 / 56 (19.64%)	3 / 20 (15.00%)
occurrences all number	0	1	0	0	6	4	3	1	0	2	0	14	3	4	11	14	6	7	11	3
Peroneal Nerve Palsy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Polyneuropathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	2
Presyncope
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1
Pyramidal Tract Syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Restless Legs Syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	5 / 25 (20.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0	1	0	0	0	0	0	1	5	0	2	0
Seizure
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Spinal Cord Compression
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0
Taste Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0
Tremor
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	4 / 10 (40.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 6 (50.00%)	0 / 3 (0.00%)	4 / 22 (18.18%)	2 / 16 (12.50%)	3 / 25 (12.00%)	4 / 25 (16.00%)	6 / 44 (13.64%)	3 / 25 (12.00%)	4 / 26 (15.38%)	11 / 56 (19.64%)	3 / 20 (15.00%)
occurrences all number	0	0	1	2	8	1	2	1	0	10	0	6	2	6	6	8	3	5	14	3
Anaemia Macrocytic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Anaemia of Chronic Disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Coagulopathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Febrile Neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Iron Deficiency Anaemia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	3 / 25 (12.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	3	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	2 / 25 (8.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	4	0	2	0	0	0	0	9	0	0	1	2	2	0	1	1
Lymphadenopathy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Lymphopenia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	2 / 25 (8.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	4 / 10 (40.00%)	2 / 11 (18.18%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	3 / 22 (13.64%)	2 / 16 (12.50%)	5 / 25 (20.00%)	7 / 25 (28.00%)	2 / 44 (4.55%)	9 / 25 (36.00%)	0 / 26 (0.00%)	7 / 56 (12.50%)	3 / 20 (15.00%)
occurrences all number	0	0	2	4	29	3	6	0	0	2	1	6	2	11	13	3	14	0	9	5
Normocytic Anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Thrombocytopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	2	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vertigo
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	1	0	0	0	0	0	0	1	0	0	1
Eye disorders
Blepharitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Borderline Glaucoma
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Cataract
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Conjunctival Haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Diplopia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Dry Eye
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	2 / 25 (8.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	1	0	0	1	0	1	1	0	0	0	0	0	0	0	1	2	2	0	2	3
Eye Irritation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Eye Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Lacrimation Increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Ocular Hyperaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Photophobia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
Photopsia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0
Trichomegaly
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Vision Blurred
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	3	0	0	0	1	1	1	0	2
Visual Impairment
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	1	0
Vitreous Floaters
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	3 / 25 (12.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	3	0	0	1	0	3	1
Abdominal Distension
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	3 / 25 (12.00%)	2 / 26 (7.69%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	0	0	3	0	0	0	0	0	2	0	0	0	3	2	2	0
Abdominal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	6 / 10 (60.00%)	4 / 11 (36.36%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 3 (33.33%)	4 / 22 (18.18%)	4 / 16 (25.00%)	8 / 25 (32.00%)	5 / 25 (20.00%)	10 / 44 (22.73%)	9 / 25 (36.00%)	7 / 26 (26.92%)	11 / 56 (19.64%)	3 / 20 (15.00%)
occurrences all number	0	0	0	0	8	7	4	0	0	3	1	7	6	8	5	10	13	13	14	3
Abdominal Pain Lower
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Abdominal Pain Upper
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 11 (9.09%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	1 / 25 (4.00%)	4 / 25 (16.00%)	2 / 44 (4.55%)	3 / 25 (12.00%)	1 / 26 (3.85%)	4 / 56 (7.14%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1	1	2	0	0	1	0	2	0	1	4	2	3	1	4	1
Ascites
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2	1	0	0	0
Cheilitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Colitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Constipation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	8 / 10 (80.00%)	7 / 11 (63.64%)	1 / 3 (33.33%)	2 / 3 (66.67%)	2 / 3 (66.67%)	4 / 6 (66.67%)	0 / 3 (0.00%)	7 / 22 (31.82%)	5 / 16 (31.25%)	12 / 25 (48.00%)	13 / 25 (52.00%)	11 / 44 (25.00%)	7 / 25 (28.00%)	11 / 26 (42.31%)	31 / 56 (55.36%)	9 / 20 (45.00%)
occurrences all number	0	0	1	1	14	10	1	2	3	8	0	9	9	15	16	13	9	13	39	9
Diarrhoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	5 / 10 (50.00%)	7 / 11 (63.64%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	4 / 6 (66.67%)	1 / 3 (33.33%)	5 / 22 (22.73%)	8 / 16 (50.00%)	10 / 25 (40.00%)	10 / 25 (40.00%)	13 / 44 (29.55%)	9 / 25 (36.00%)	11 / 26 (42.31%)	20 / 56 (35.71%)	6 / 20 (30.00%)
occurrences all number	0	0	0	1	11	13	1	4	0	9	1	7	10	13	21	17	10	18	28	6
Dry Mouth
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	3 / 22 (13.64%)	0 / 16 (0.00%)	1 / 25 (4.00%)	3 / 25 (12.00%)	5 / 44 (11.36%)	2 / 25 (8.00%)	5 / 26 (19.23%)	2 / 56 (3.57%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	3	0	1	3	5	3	8	2	3
Duodenogastric Reflux
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Dyspepsia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	2 / 11 (18.18%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	1 / 16 (6.25%)	3 / 25 (12.00%)	4 / 25 (16.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	2 / 26 (7.69%)	2 / 56 (3.57%)	2 / 20 (10.00%)
occurrences all number	0	0	0	2	2	2	1	0	0	1	0	2	1	3	4	2	0	2	2	2
Dysphagia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	2	1	0	0	1
Epigastric Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Eructation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Flatulence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	2 / 26 (7.69%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	2	2	0
Gastric Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Gastritis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Gastrointestinal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 22 (4.55%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	2 / 25 (8.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	1	0	1	0	0	2	0	3	0
Gingival Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Gingival Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Haematochezia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Haemorrhoids
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	1	0	0
Hiatus Hernia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hyperaesthesia Teeth
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Impaired Gastric Emptying
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Intestinal Obstruction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Nausea
subjects affected / exposed	1 / 1 (100.00%)	1 / 1 (100.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	6 / 10 (60.00%)	7 / 11 (63.64%)	3 / 3 (100.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	4 / 6 (66.67%)	2 / 3 (66.67%)	14 / 22 (63.64%)	10 / 16 (62.50%)	11 / 25 (44.00%)	15 / 25 (60.00%)	13 / 44 (29.55%)	15 / 25 (60.00%)	11 / 26 (42.31%)	22 / 56 (39.29%)	6 / 20 (30.00%)
occurrences all number	1	1	1	4	9	17	7	0	2	6	2	18	12	12	20	19	22	16	30	7
Neutropenic Colitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Pancreatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Proctalgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Retching
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0
Salivary Duct Inflammation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Stomatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	2	0	1	0	0
Toothache
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Vomiting
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	6 / 10 (60.00%)	7 / 11 (63.64%)	3 / 3 (100.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	6 / 22 (27.27%)	3 / 16 (18.75%)	4 / 25 (16.00%)	6 / 25 (24.00%)	9 / 44 (20.45%)	7 / 25 (28.00%)	7 / 26 (26.92%)	15 / 56 (26.79%)	4 / 20 (20.00%)
occurrences all number	0	1	0	4	13	11	6	1	0	3	3	6	3	4	10	15	8	16	21	4
Hepatobiliary disorders
Biliary Colic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Cholangitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hepatic Failure
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hepatic Steatosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hepatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Jaundice
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	3 / 11 (27.27%)	3 / 3 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	4 / 22 (18.18%)	5 / 16 (31.25%)	7 / 25 (28.00%)	8 / 25 (32.00%)	3 / 44 (6.82%)	9 / 25 (36.00%)	6 / 26 (23.08%)	14 / 56 (25.00%)	2 / 20 (10.00%)
occurrences all number	0	0	0	1	2	3	3	0	0	2	0	4	5	7	9	3	9	6	14	2
Blister
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Dermatitis Allergic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Dermatitis Bullous
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Dermatitis Contact
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Dry Skin
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	2 / 26 (7.69%)	2 / 56 (3.57%)	2 / 20 (10.00%)
occurrences all number	0	0	0	1	0	1	1	0	0	0	0	1	0	2	0	2	0	2	2	2
Ecchymosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Eczema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Erythema
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Erythema Multiforme
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hair Texture Abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hyperhidrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	1	0	0	2	0
Lichenoid Keratosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Nail Discolouration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Nail Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Nail Dystrophy
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Night Sweats
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	2	1	3
Onychoclasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Pruritus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	3 / 16 (18.75%)	4 / 25 (16.00%)	1 / 25 (4.00%)	6 / 44 (13.64%)	3 / 25 (12.00%)	3 / 26 (11.54%)	6 / 56 (10.71%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	1	1	0	0	0	0	0	2	4	4	2	7	4	3	7	1
Psoriasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Rash
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	2 / 25 (8.00%)	5 / 44 (11.36%)	2 / 25 (8.00%)	3 / 26 (11.54%)	6 / 56 (10.71%)	3 / 20 (15.00%)
occurrences all number	0	0	1	0	1	1	0	1	0	0	0	0	1	0	3	5	2	5	7	4
Rash Erythematous
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0	0	0	0
Rash Macular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Rash Maculo-papular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Rash Pruritic
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	2 / 25 (8.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Skin Disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Skin Hyperpigmentation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Skin Irritation
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Skin Lesion
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Skin Mass
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Skin Reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Renal and urinary disorders
Acute Kidney Injury
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	2 / 25 (8.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	2	0	0	0
Bladder Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Calculus Bladder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Dysuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	1	1	1
Haematuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	1	0	2	1
Hydronephrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hypertonic Bladder
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Nocturia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Pollakiuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1
Polyuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Proteinuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Urge Incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Urinary Incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Urinary Retention
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Endocrine disorders
Adrenal Insufficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	2	0
Hyperthyroidism
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Hypothyroidism
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	4 / 22 (18.18%)	1 / 16 (6.25%)	3 / 25 (12.00%)	7 / 25 (28.00%)	6 / 44 (13.64%)	2 / 25 (8.00%)	5 / 26 (19.23%)	8 / 56 (14.29%)	2 / 20 (10.00%)
occurrences all number	1	0	0	0	0	0	1	0	0	2	0	6	1	3	9	6	3	5	13	2
Arthritis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	2	0
Back Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 10 (20.00%)	3 / 11 (27.27%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	2 / 22 (9.09%)	0 / 16 (0.00%)	4 / 25 (16.00%)	1 / 25 (4.00%)	6 / 44 (13.64%)	2 / 25 (8.00%)	3 / 26 (11.54%)	9 / 56 (16.07%)	1 / 20 (5.00%)
occurrences all number	0	0	2	1	2	4	0	0	0	1	0	6	0	4	1	6	2	4	10	1
Bone Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	2 / 25 (8.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	2	1	0	1	0	1	0
Bursitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Fistula
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Flank Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	2	0	2	1	0
Groin Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0
Joint Range of Motion Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0	0
Limb Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Mobility Decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Muscle Spasms
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	4 / 22 (18.18%)	0 / 16 (0.00%)	2 / 25 (8.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	4	0	0	0	0	1	0	0	0	0	5	0	2	2	1	0	0	2	0
Muscle Tightness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Muscular Weakness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	1	1	1	0	2	1	0
Musculoskeletal Chest Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	2 / 25 (8.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0	1	1	0
Musculoskeletal Discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	1	0
Musculoskeletal Stiffness
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Myalgia
subjects affected / exposed	1 / 1 (100.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	2 / 22 (9.09%)	4 / 16 (25.00%)	4 / 25 (16.00%)	5 / 25 (20.00%)	4 / 44 (9.09%)	3 / 25 (12.00%)	3 / 26 (11.54%)	4 / 56 (7.14%)	5 / 20 (25.00%)
occurrences all number	1	0	1	2	0	0	0	0	0	3	0	2	6	5	6	4	3	3	4	6
Neck Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	1	1	0	1	0	1	1	0
Pain in Extremity
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	3 / 22 (13.64%)	5 / 16 (31.25%)	0 / 25 (0.00%)	2 / 25 (8.00%)	1 / 44 (2.27%)	2 / 25 (8.00%)	2 / 26 (7.69%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	3	6	0	3	1	2	2	3	1
Polyarthritis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Spinal Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Infections and infestations
Bacteriuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Bronchiolitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Bronchitis
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
COVID-19
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Candida Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Cellulitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Citrobacter Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Conjunctivitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Cystitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	1	1	0	2	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Cystitis Escherichia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Epididymitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Escherichia Urinary Tract Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Eye Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Fungal Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Fungal Oesophagitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Gastroenteritis Viral
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0
Herpes Simplex
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Herpes Zoster
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0
Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Influenza
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Lower Respiratory Tract Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	2	1
Lung Abscess
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Nasopharyngitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	0 / 11 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	1	4	0	1	0	0	0	0	0	1	1	0	1	0	0	0	0
Oral Candidiasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	2 / 25 (8.00%)	2 / 44 (4.55%)	1 / 25 (4.00%)	0 / 26 (0.00%)	5 / 56 (8.93%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	2	1	0	0	0	2	1	0	0	1	2	2	1	0	5	0
Parainfluenzae Virus Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Paronychia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Pneumonia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	1 / 16 (6.25%)	0 / 25 (0.00%)	2 / 25 (8.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	3 / 26 (11.54%)	0 / 56 (0.00%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	1	0	2	1	1	6	0	1
Pyuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Rash Pustular
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Rhinitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Sinusitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Skin Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Tooth Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	1	0	0
Upper Respiratory Tract Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	2 / 56 (3.57%)	1 / 20 (5.00%)
occurrences all number	0	0	1	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	2	1
Urinary Tract Candidiasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Urinary Tract Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 11 (18.18%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	3 / 22 (13.64%)	1 / 16 (6.25%)	3 / 25 (12.00%)	1 / 25 (4.00%)	1 / 44 (2.27%)	1 / 25 (4.00%)	1 / 26 (3.85%)	6 / 56 (10.71%)	2 / 20 (10.00%)
occurrences all number	0	0	0	1	0	2	5	0	0	3	0	4	1	3	1	5	1	1	8	2
Vaginal Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Viral Infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	3 / 10 (30.00%)	8 / 11 (72.73%)	2 / 3 (66.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 6 (50.00%)	1 / 3 (33.33%)	8 / 22 (36.36%)	8 / 16 (50.00%)	5 / 25 (20.00%)	8 / 25 (32.00%)	14 / 44 (31.82%)	7 / 25 (28.00%)	12 / 26 (46.15%)	26 / 56 (46.43%)	7 / 20 (35.00%)
occurrences all number	0	1	0	3	3	12	5	1	0	4	1	10	8	6	11	14	7	16	31	7
Dehydration
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	4 / 56 (7.14%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	4	1
Fluid Overload
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hypercalcaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	0 / 25 (0.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	1	0	0	3	1
Hypercholesterolaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	3 / 22 (13.64%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 3 (66.67%)	2 / 22 (9.09%)	0 / 16 (0.00%)	2 / 25 (8.00%)	0 / 25 (0.00%)	1 / 44 (2.27%)	2 / 25 (8.00%)	2 / 26 (7.69%)	1 / 56 (1.79%)	2 / 20 (10.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	2	2	0	4	0	1	2	3	1	2
Hyperkalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	1 / 20 (5.00%)
occurrences all number	0	0	0	2	0	3	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hypermagnesaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 22 (4.55%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hypernatraemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	1 / 16 (6.25%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 11 (9.09%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	2 / 22 (9.09%)	2 / 16 (12.50%)	2 / 25 (8.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	2 / 56 (3.57%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	3	2	0	0	0	0	1	2	6	4	2	0	0	1	3	0
Hyperuricaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	1 / 25 (4.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	3 / 22 (13.64%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	2 / 44 (4.55%)	1 / 25 (4.00%)	0 / 26 (0.00%)	3 / 56 (5.36%)	1 / 20 (5.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	3	0	0	0	2	1	0	3	1
Hypocalcaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	4 / 22 (18.18%)	0 / 16 (0.00%)	1 / 25 (4.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	2	4	0	2	1	2	0	0	1	0
Hypoglycaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (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
Hypokalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 3 (66.67%)	3 / 10 (30.00%)	3 / 11 (27.27%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	7 / 22 (31.82%)	2 / 16 (12.50%)	2 / 25 (8.00%)	3 / 25 (12.00%)	3 / 44 (6.82%)	2 / 25 (8.00%)	3 / 26 (11.54%)	12 / 56 (21.43%)	3 / 20 (15.00%)
occurrences all number	0	0	0	2	3	6	2	0	0	1	1	8	2	4	3	5	2	5	17	5
Hypomagnesaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	2 / 11 (18.18%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	3 / 22 (13.64%)	1 / 16 (6.25%)	3 / 25 (12.00%)	0 / 25 (0.00%)	3 / 44 (6.82%)	2 / 25 (8.00%)	3 / 26 (11.54%)	10 / 56 (17.86%)	1 / 20 (5.00%)
occurrences all number	0	0	0	1	4	2	0	0	0	1	1	3	1	4	0	3	2	6	20	2
Hyponatraemia
subjects affected / exposed	0 / 1 (0.00%)	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 11 (27.27%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	2 / 22 (9.09%)	0 / 16 (0.00%)	3 / 25 (12.00%)	1 / 25 (4.00%)	2 / 44 (4.55%)	2 / 25 (8.00%)	4 / 26 (15.38%)	6 / 56 (10.71%)	2 / 20 (10.00%)
occurrences all number	0	2	0	0	0	7	2	0	0	0	1	2	0	4	1	2	2	6	11	3
Hypophagia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Hypophosphataemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	2 / 22 (9.09%)	0 / 16 (0.00%)	0 / 25 (0.00%)	2 / 25 (8.00%)	3 / 44 (6.82%)	0 / 25 (0.00%)	0 / 26 (0.00%)	4 / 56 (7.14%)	2 / 20 (10.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	2	0	0	3	3	0	0	7	2
Iron Deficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	1 / 25 (4.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	0 / 56 (0.00%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Malnutrition
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (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
Polydipsia
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Type 2 Diabetes Mellitus
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	0 / 25 (0.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	1 / 26 (3.85%)	0 / 56 (0.00%)	0 / 20 (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
Vitamin D Deficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 11 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 22 (0.00%)	0 / 16 (0.00%)	1 / 25 (4.00%)	0 / 25 (0.00%)	0 / 44 (0.00%)	0 / 25 (0.00%)	0 / 26 (0.00%)	1 / 56 (1.79%)	0 / 20 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

16 Dec 2016

Included melanoma cancer as an additional indication in the trial. Inclusion/exclusion criteria were updated. Genetic and proteomic analyses were removed. Updated and clarified the sampling, timing, specification, handling and methods of the exploratory analyses. Storage of the biological samples in the trial was clarified.

25 Sep 2017

Introduced the updated mitigation plan for handling of constipation and introduced safety blood samples collected locally 24 hours prior to each study drug administration. Clarified the visit window of Cycle 2 Visit 1 in order to ensure that the DLT evaluation period during Cycle 1 completed as planned before initiation of Cycle 2. Updated time windows for some of the assessments of vital signs in order to allow for practical and safe assessments.

12 Apr 2018

An arm with platinum-resistant ovarian cancer participants was added to the Expansion part of the trial; this also increased the planned number of participants. An interim analysis for futility for all cohorts was introduced, which provided a mechanism to reduce the number of participants exposed to a potentially inefficient experimental therapy. Participants who benefit from the treatment were offered continued treatment within the scope of the protocol until their disease progressed or until they experienced unacceptable toxicity. A subject diary was introduced in order to capture information on prophylactic use of stool softeners to prevent constipation. The diary also captured changes in stool frequency and consistency.

11 Oct 2018

Additional participants to be enrolled in Cohort 2 were added due to observation of an efficacy signal in participants without drug-sensitizing mutations treated for NSCLC. Clarified that in Cohort 2, only participants with wild-type EGFR should be enrolled, ie, not only participants without the classical sensitizing EGFR mutations but also without the resistance mutations such as T790M, targeted by third generation tyrosine kinase inhibitors (TKIs). Newly identified risks, including peripheral neuropathy and neutropenia, were described for enapotamab vedotin in Version 4.0 of the Investigator’s Brochure (IB). Based on this IB update, new participants were added describing the relevant safety findings. Changed the INN name for HuMax-AXL-ADC to enapotamab vedotin. Expansion part 'cohort(s)' used throughout the protocol instead of arm(s).

07 Dec 2018

Modified some of the inclusion criteria for the expansion cohorts to further define the exact target subject population and to guard participant safety during the study. Due to emerging safety data, a new subsection on dose modifications for immune-related AEs (irAEs) was introduced for optimal management of these events. The possibility to conduct further safety review after 36 and 100 participants in the Expansion part was added.

18 Jun 2019

Excluded participants with ongoing pneumonitis at Screening or with a history of noninfectious pneumonitis that required steroids. Allowed for inclusion of participants who had pneumonitis (asymptomatic, did not require steroid treatment, and had no radiological evidence) in the past if more than 6 months prior to enrollment. Increased the treatment interruption window period to maximize the clinical benefit for participants. Clarified that every effort should be made to document disease progression by radiological imaging and RECIST even though participant was discontinued from trial treatment (eg, due to an AE). Based on negative emerging data that showed absence of AXL+ circulating tumor cells (CTCs) in post-PD(L)1 NSCLC participants, CTC assessments were no longer considered useful evaluating this trial drug. Clarified text around confirmation of response according to RECIST and guidance added around scans in case of discontinuation due to an AE. Clarified timing of scans and unscheduled scans. Clarified that both investigator disease assessments as well as Independent Review Committee assessment would be used for analysis. Added clarification on expectations where bronchoscopy-guided biopsies were allowed. Noted that the information on investigator assessment of the clinical significance of laboratory values was not included in the Study Data Tabulation Model dataset and therefore could not be extracted for inclusion in listings. The treatment algorithm was changed from a limited number of cycles to treatment until progression of the underlying disease per RECIST was detected.

21 Oct 2019

Implemented more stringent dose modification guidance for TEAEs of peripheral neuropathy. Modified PK sampling. In an attempt to improve the observed tolerability profile and expand the possible therapeutic window for enapotamab vedotin, a limited number of participants could be enrolled in Cohort 2 on a starting dose of 1.8 mg/kg. In order to obtain 25 fresh biopsies from Cohort 6, up to 15 additional participants could be recruited. Implemented to further explore the potential of the maximum tolerated dose (MTD) of the 3Q4W schedule. Clarified that adjuvant or maintenance treatment would be counted as 1 regimen, together with the relevant surgery or primary treatment. Revised inclusion criteria as the reference to adjuvant and maintenance treatment was no longer relevant for the inclusion criterion. Relaxed the restriction criteria, as the restriction of up to 3 lines of prior treatment proved to be challenging for enrollment as many participants failed more than 3 lines. Clarified how long dosing could be delayed for and how the resumption of dosing should be handled for the 3Q4W dosing schedule. Spain was included as a country in the trial.

09 Dec 2019

Added Cohort 8 to further explore, in the same participant population as Cohort 2, the 1.0 mg/kg 3Q4W schedule adding up to 37 participants to be treated. Added a rationale for the subgroup of the participants in Cohort 2 at a dose of 1.8 mg/kg, which was not included in Amendment dated 21 October 2019. Excluded participants who experienced hyper-progressive disease during prior checkpoint inhibitor therapy. Reduced number of visits as visits were a burden for participants. Clarified PK assessments for Expansion. Added peripheral neuropathy reporting requirements to enhance data collection and facilitate the understanding and characterization of the event. Clarified data summarized for participants with NSCLC without EGFR/ALK mutations. Removed interim analysis for futility for Cohorts 6 and 8.

30 Jun 2021

To allow analysis and reporting of the trial, while permitting the 3 remaining participants to stay on treatment and be followed per protocol. At the time of this Amendment, the Dose Escalation part and the enrollment of the Expansion part of trial had been completed; 3 participants remained on treatment. The 3 participants had been on treatment for at least 7 months, which was considered sufficient to evaluate efficacy and safety. With this amendment, the 3 participants still on treatment continued treatment and were followed with reduced procedures and visits. Sections Statistical Analysis, Interim Analyses, and Clinical Trial Reporting were revised to reflect the analysis of efficacy and safety per data cut-off date and clinical trial reporting plans. The plan to present corrected QT interval analyses in a separate report was removed.

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.

No participants with castration-resistant prostate cancer were enrolled, hence no prostate-specific antigen (PSA) data were available and pre-specified outcome measure related to PSA data are not reported.

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Clinical trials

Clinical Trial Results: First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Dose-limiting Toxicities (DLTs) for Dose-escalation Part

Primary: Number of Participants With Dose-limiting Toxicities (DLTs) for Dose-escalation Part

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

Primary: Number of Participants With Treatment-emergent Infusion-related AEs and TEAEs Related to Enapotamab Vedotin

Primary: Number of Participants With Treatment-emergent Infusion-related AEs and TEAEs Related to Enapotamab Vedotin

Primary: Number of Participants With >= Grade 3 TEAEs as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

Primary: Number of Participants With >= Grade 3 TEAEs as Assessed by National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

Secondary: Number of Participants With Grade 3 or 4 Laboratory Results

Secondary: Number of Participants With Grade 3 or 4 Laboratory Results

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUC0-last) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Maximum Observed Plasma Concentration (Cmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Maximum Observed Plasma Concentration (Cmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Total Clearance (CL) of Conjugated Enapotamab Vedotin in Dose-escalation Part

Secondary: Total Clearance (CL) of Conjugated Enapotamab Vedotin in Dose-escalation Part

Secondary: Time of Maximum Plasma Concentration (Tmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Time of Maximum Plasma Concentration (Tmax) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Half-life Lambda-z (t1/2) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Half-life Lambda-z (t1/2) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Volume of Distribution at Steady State (Vss) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: Volume of Distribution at Steady State (Vss) of Conjugated Enapotamab Vedotin for Dose-escalation Part

Secondary: AUC0-inf of Free Toxin Monomethyl Auristatin E (MMAE) for Dose-escalation Part

Secondary: AUC0-inf of Free Toxin Monomethyl Auristatin E (MMAE) for Dose-escalation Part

Secondary: AUC0-last of MMAE for Dose-escalation Part

Secondary: AUC0-last of MMAE for Dose-escalation Part

Secondary: Cmax of MMAE for Dose-escalation Part

Secondary: Cmax of MMAE for Dose-escalation Part

Secondary: Total CL of MMAE in Dose-escalation Part

Secondary: Total CL of MMAE in Dose-escalation Part

Secondary: Tmax of MMAE for Dose-escalation Part

Secondary: Tmax of MMAE for Dose-escalation Part

Secondary: t1/2 of MMAE for Dose-escalation Part

Secondary: t1/2 of MMAE for Dose-escalation Part

Secondary: Number of Participants With Antidrug Antibodies (ADAs) Confirmed Positive to Enapotamab Vedotin

Secondary: Number of Participants With Antidrug Antibodies (ADAs) Confirmed Positive to Enapotamab Vedotin

Secondary: Number of Participants With Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) As Assessed by Investigator

Secondary: Number of Participants With Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) As Assessed by Investigator

Secondary: Number of Participants With Best Cancer Antigen 125 (CA-125) Response

Secondary: Number of Participants With Best Cancer Antigen 125 (CA-125) Response

Secondary: Duration of Response (DoR) Based on RECIST v1.1 as Assessed by Investigator for Expansion Part

Secondary: Duration of Response (DoR) Based on RECIST v1.1 as Assessed by Investigator for Expansion Part

Secondary: Progression Free Survival (PFS) as Assessed by Investigator

Secondary: Progression Free Survival (PFS) as Assessed by Investigator

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Change in AXL Expression (Total Tumor H-score) From Baseline to EOT Visit for Expansion Part

Secondary: Change in AXL Expression (Total Tumor H-score) From Baseline to EOT Visit for Expansion Part

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of Axl-specific Antibody-drug Conjugate (Enapotamab Vedotin, HuMax®-AXL-ADC) in Patients With Solid Tumors