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Clinical Trial Results:
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)

Summary
EudraCT number	2017-000625-12
Trial protocol	NL ES DE
Global end of trial date	10 Sep 2020

Results information
Results version number	v1(current)
This version publication date	17 Oct 2021
First version publication date	17 Oct 2021
Other versions

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

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Trial information

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Sponsor protocol code

CTMX-M-2009-001

ISRCTN number

US NCT number

NCT03149549

WHO universal trial number (UTN)

Sponsor organisation name

CytomX Therapeutics, Inc

Sponsor organisation address

151 Oyster Point Blvd, South San Francisco, United States, 94080

Public contact

Clinical Trial Team, CytomX Therapeutics, Inc, 001 650-763-9501, clinicaltrials@cytomx.com

Scientific contact

Clinical Development, CytomX Therapeutics, Inc, 001 650-515-3185, clinicaltrials@cytomx.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

17 Nov 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Sep 2020

Global end of trial reached?

Yes

Global end of trial date

10 Sep 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

The primary objective of the study is to determine the safety profile of CX-2009, the maximum tolerated dose (MTD) / Recommended Phase 2 Dose (RP2D), and the dose-limiting toxicities (DLTs) of CX-2009, when administered intravenously (IV) every 21 days as monotherapy to subjects with selected advanced or recurrent solid tumors.

Protection of trial subjects

This study was conducted in full accordance with the World Medical Association Declaration of Helsinki concerning written informed consent and the protection of rights of human subjects. The investigators agreed to comply with Food and Drug Administration (FDA) Regulations, IRB/IEC Regulations and International Council of Harmonisation (ICH) Guidelines for Good Clinical Practices (GCP).

Background therapy

Evidence for comparator

Actual start date of recruitment

15 May 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 64

Country: Number of subjects enrolled

Netherlands: 2

Country: Number of subjects enrolled

Spain: 24

Country: Number of subjects enrolled

United Kingdom: 9

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted in 4 parts (Part A, Part A2, Part B, and Part C1). Enrolled patients continued on study through the follow-up period. Each study part consisted of 3 periods: a 30-day screening, a treatment period, and a follow-up period.

Screening details

As of 09/April/2020, 99 patients had been enrolled and treated in the study (47 in Part A, 39 in Part A2, 3 in Part B, and 10 in Part C1); enrolled patients continued on study through the follow-up period. The study was terminated early after these subjects were enrolled.

Period 1 title

Study Treatment Period

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dose Group 1 (≤ 4 mg/kg (Q3W))

Arm description

less than or equal to 4 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 2 (5 mg/kg (Q3W))

Arm description

5 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 3 (6 mg/kg (Q3W))

Arm description

6 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 4 (7 mg/kg (Q3W))

Arm description

7 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 5 (8 mg/kg (Q3W))

Arm description

8 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 6 (9 mg/kg (Q3W))

Arm description

9 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 7 (10 mg/kg (Q3W))

Arm description

10 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 8 (4 mg/kg (Q2W))

Arm description

4 mg/kg (Q2W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 9 (6 mg/kg (Q2W))

Arm description

6 mg/kg (Q2W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Number of subjects in period 1	Dose Group 1 (≤ 4 mg/kg (Q3W))	Dose Group 2 (5 mg/kg (Q3W))	Dose Group 3 (6 mg/kg (Q3W))	Dose Group 4 (7 mg/kg (Q3W))	Dose Group 5 (8 mg/kg (Q3W))	Dose Group 6 (9 mg/kg (Q3W))	Dose Group 7 (10 mg/kg (Q3W))	Dose Group 8 (4 mg/kg (Q2W))	Dose Group 9 (6 mg/kg (Q2W))
Started	20	9	9	12	22	9	8	4	6
Completed	14	7	7	8	16	7	8	4	4
Not completed	6	2	2	4	6	2	0	0	2
Adverse event, serious fatal	3	1	-	2	4	1	-	-	1
Termination by Sponsor	-	-	-	1	-	-	-	-	1
Consent withdrawn by subject	3	1	2	-	2	-	-	-	-
Unknown	-	-	-	1	-	1	-	-	-

Period 2 title

Follow-Up Period

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dose Group 1 (≤ 4 mg/kg (Q3W))

Arm description

less than or equal to 4 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 2 (5 mg/kg (Q3W))

Arm description

5 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 3 (6 mg/kg (Q3W))

Arm description

6 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 4 (7 mg/kg (Q3W))

Arm description

7 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 5 (8 mg/kg (Q3W))

Arm description

8 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 6 (9 mg/kg (Q3W))

Arm description

9 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 7 (10 mg/kg (Q3W))

Arm description

10 mg/kg (Q3W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 8 (4 mg/kg (Q2W))

Arm description

4 mg/kg (Q2W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Dose Group 9 (6 mg/kg (Q2W))

Arm description

6 mg/kg (Q2W)

Arm type

Experimental

Investigational medicinal product name

CX-2009

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection/infusion

Routes of administration

Infusion

Dosage and administration details

CX-2009 was supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of sterile water for injection to a final concentration of 5.0 mg/mL

Number of subjects in period 2	Dose Group 1 (≤ 4 mg/kg (Q3W))	Dose Group 2 (5 mg/kg (Q3W))	Dose Group 3 (6 mg/kg (Q3W))	Dose Group 4 (7 mg/kg (Q3W))	Dose Group 5 (8 mg/kg (Q3W))	Dose Group 6 (9 mg/kg (Q3W))	Dose Group 7 (10 mg/kg (Q3W))	Dose Group 8 (4 mg/kg (Q2W))	Dose Group 9 (6 mg/kg (Q2W))
Started	14	7	7	8	16	7	8	4	4
Completed	12	3	6	3	9	5	5	1	1
Not completed	2	4	1	5	7	2	3	3	3
Termination by Sponsor	1	-	-	1	5	-	-	3	2
Consent withdrawn by subject	1	-	-	4	1	1	3	-	1
Unknown	-	-	-	-	-	1	-	-	-
Lost to follow-up	-	4	1	-	1	-	-	-	-

Baseline characteristics

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Reporting group title

Dose Group 1 (≤ 4 mg/kg (Q3W))

Reporting group description

less than or equal to 4 mg/kg (Q3W)

Reporting group title

Dose Group 2 (5 mg/kg (Q3W))

Reporting group description

5 mg/kg (Q3W)

Reporting group title

Dose Group 3 (6 mg/kg (Q3W))

Reporting group description

6 mg/kg (Q3W)

Reporting group title

Dose Group 4 (7 mg/kg (Q3W))

Reporting group description

7 mg/kg (Q3W)

Reporting group title

Dose Group 5 (8 mg/kg (Q3W))

Reporting group description

8 mg/kg (Q3W)

Reporting group title

Dose Group 6 (9 mg/kg (Q3W))

Reporting group description

9 mg/kg (Q3W)

Reporting group title

Dose Group 7 (10 mg/kg (Q3W))

Reporting group description

10 mg/kg (Q3W)

Reporting group title

Dose Group 8 (4 mg/kg (Q2W))

Reporting group description

4 mg/kg (Q2W)

Reporting group title

Dose Group 9 (6 mg/kg (Q2W))

Reporting group description

6 mg/kg (Q2W)

Reporting group values	Dose Group 1 (≤ 4 mg/kg (Q3W))	Dose Group 2 (5 mg/kg (Q3W))	Dose Group 3 (6 mg/kg (Q3W))	Dose Group 4 (7 mg/kg (Q3W))	Dose Group 5 (8 mg/kg (Q3W))	Dose Group 6 (9 mg/kg (Q3W))	Dose Group 7 (10 mg/kg (Q3W))	Dose Group 8 (4 mg/kg (Q2W))	Dose Group 9 (6 mg/kg (Q2W))	Total
Number of subjects	20	9	9	12	22	9	8	4	6	99
Age categorical
Adult Subjects of at least 18 years of age and older
Units: Subjects
In utero	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
Newborns (0-27 days)	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
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	11	7	5	7	15	5	7	3	5	65
From 65-84 years	9	2	4	5	7	4	1	1	1	34
85 years and over	0	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	13	7	6	12	18	7	7	4	4	78
Male	7	2	3	0	4	2	1	0	2	21
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0
Asian	2	0	0	1	2	0	0	0	0	5
Native Hawaiian or Other Pacific Islander	0	0	0	1	1	0	0	0	0	2
Black or African American	0	0	0	0	0	2	0	0	0	2
White	18	8	8	6	17	7	7	4	6	81
More than one race	0	1	0	0	1	0	1	0	0	3
Unknown or Not Reported	0	0	1	4	1	0	0	0	0	6
Ethnicity
Units: Subjects
Hispanic or Latino	1	2	0	1	1	2	1	0	0	8
Not Hispanic or Latino	18	7	8	9	20	7	7	4	6	86
Unknown or Not Reported	1	0	1	2	1	0	0	0	0	5

End points

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Reporting group title

Dose Group 1 (≤ 4 mg/kg (Q3W))

Reporting group description

less than or equal to 4 mg/kg (Q3W)

Reporting group title

Dose Group 2 (5 mg/kg (Q3W))

Reporting group description

5 mg/kg (Q3W)

Reporting group title

Dose Group 3 (6 mg/kg (Q3W))

Reporting group description

6 mg/kg (Q3W)

Reporting group title

Dose Group 4 (7 mg/kg (Q3W))

Reporting group description

7 mg/kg (Q3W)

Reporting group title

Dose Group 5 (8 mg/kg (Q3W))

Reporting group description

8 mg/kg (Q3W)

Reporting group title

Dose Group 6 (9 mg/kg (Q3W))

Reporting group description

9 mg/kg (Q3W)

Reporting group title

Dose Group 7 (10 mg/kg (Q3W))

Reporting group description

10 mg/kg (Q3W)

Reporting group title

Dose Group 8 (4 mg/kg (Q2W))

Reporting group description

4 mg/kg (Q2W)

Reporting group title

Dose Group 9 (6 mg/kg (Q2W))

Reporting group description

6 mg/kg (Q2W)

Reporting group title

Dose Group 1 (≤ 4 mg/kg (Q3W))

Reporting group description

less than or equal to 4 mg/kg (Q3W)

Reporting group title

Dose Group 2 (5 mg/kg (Q3W))

Reporting group description

5 mg/kg (Q3W)

Reporting group title

Dose Group 3 (6 mg/kg (Q3W))

Reporting group description

6 mg/kg (Q3W)

Reporting group title

Dose Group 4 (7 mg/kg (Q3W))

Reporting group description

7 mg/kg (Q3W)

Reporting group title

Dose Group 5 (8 mg/kg (Q3W))

Reporting group description

8 mg/kg (Q3W)

Reporting group title

Dose Group 6 (9 mg/kg (Q3W))

Reporting group description

9 mg/kg (Q3W)

Reporting group title

Dose Group 7 (10 mg/kg (Q3W))

Reporting group description

10 mg/kg (Q3W)

Reporting group title

Dose Group 8 (4 mg/kg (Q2W))

Reporting group description

4 mg/kg (Q2W)

Reporting group title

Dose Group 9 (6 mg/kg (Q2W))

Reporting group description

6 mg/kg (Q2W)

Primary: The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy

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End point title

The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy ^[1]

End point description

Determine the safety profile of CX-2009, the MTD/RP2D, and the DLTs of CX-2009 when administered IV every 14 or 21 days as monotherapy to participants with selected advanced or recurrent solid tumors. Adverse event collection and assessment will be evaluated for all participants receiving study drug to evaluate the safety, tolerability, and determine DLTs at MTD/RP2D.

End point type

Primary

End point timeframe

Every 14 or 21 days (dose limiting toxicity period)

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: The study was terminated early, but the RP2D was determined for CX-2009. The study commenced with accelerated dose titration in 1 single-subject cohort (0.25 mg/kg AIBQ), followed by a standard 3+3 design to determine the MTD, and then concluded using a Bayesian interval dose-finding design (mTPI-2) cohort with up to 38 subjects with demonstrated high CD166 expression to determine the RP2D. No other statistical analyses were done.

End point values	Dose Group 1 (≤ 4 mg/kg (Q3W))	Dose Group 2 (5 mg/kg (Q3W))	Dose Group 3 (6 mg/kg (Q3W))	Dose Group 4 (7 mg/kg (Q3W))	Dose Group 5 (8 mg/kg (Q3W))	Dose Group 6 (9 mg/kg (Q3W))	Dose Group 7 (10 mg/kg (Q3W))	Dose Group 8 (4 mg/kg (Q2W))	Dose Group 9 (6 mg/kg (Q2W))
Number of subjects analysed	20	9	9	12	22	9	8	4	6
Units: Subjects
Participants experiencing DLTs	0	0	0	0	1	0	0	0	2
Participants not experiencing DLTs	20	9	9	12	21	9	8	4	4

No statistical analyses for this end point

Secondary: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy

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End point title

The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy ^[2]

End point description

Evaluate the efficacy of CX-2009 when administered IV every 21 days as monotherapy at the MTD/RP2D. Efficacy will be assessed via objective response rate (ORR) by RECIST version 1.1. ORR is defined as the proportion of patients with complete resonse (CR) or partial response (PR) on two consecutive tumor assessments with scan dates at least 4 weeks apart according to RECIST (version 1.1)

End point type

Secondary

End point timeframe

2 Years

Notes
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This study was terminated early due to the Covid Pandemic and the company's business decision to separate the Phase 2 (part B) course of the study to a separate, new Phase 2 study. The Phase 1 (part A) course of the study was completed and the RP2D was determined. Part B only enrolled 3 patients and the Secondary (ORR) and other Outcomes were not analyzed.

End point values	Dose Group 4 (7 mg/kg (Q3W))
Number of subjects analysed	3
Units: Not analysed	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Timeframe for AE

Adverse event reporting additional description

AE additional description

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Dosing Group 1 (≤ 4 mg/kg (Q3W))

Reporting group description

less than or equal to 4 mg/kg (Q3W)

Reporting group title

Dosing Group 2 (5 mg/kg (Q3W))

Reporting group description

5 mg/kg (Q3W)

Reporting group title

Dosing Group 3 (6 mg/kg (Q3W))

Reporting group description

6 mg/kg (Q3W)

Reporting group title

Dosing Group 4 (7 mg/kg (Q3W))

Reporting group description

7 mg/kg (Q3W)

Reporting group title

Dosing Group 5 (8 mg/kg (Q3W))

Reporting group description

8 mg/kg (Q3W)

Reporting group title

Dosing Group 6 (9 mg/kg (Q3W))

Reporting group description

9 mg/kg (Q3W)

Reporting group title

Dosing Group 7 (10 mg/kg (Q3W))

Reporting group description

10 mg/kg (Q3W)

Reporting group title

Dosing Group 8 (4 mg/kg (Q2W))

Reporting group description

4 mg/kg (Q2W)

Reporting group title

Dosing Group 9 (6 mg/kg (Q2W))

Reporting group description

6 mg/kg (Q2W)

Serious adverse events	Dosing Group 1 (≤ 4 mg/kg (Q3W))	Dosing Group 2 (5 mg/kg (Q3W))	Dosing Group 3 (6 mg/kg (Q3W))	Dosing Group 4 (7 mg/kg (Q3W))	Dosing Group 5 (8 mg/kg (Q3W))	Dosing Group 6 (9 mg/kg (Q3W))	Dosing Group 7 (10 mg/kg (Q3W))	Dosing Group 8 (4 mg/kg (Q2W))	Dosing Group 9 (6 mg/kg (Q2W))
Total subjects affected by serious adverse events
subjects affected / exposed	3 / 20 (15.00%)	2 / 9 (22.22%)	3 / 9 (33.33%)	5 / 12 (41.67%)	10 / 22 (45.45%)	5 / 9 (55.56%)	4 / 8 (50.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
number of deaths (all causes)	0	0	0	1	1	1	1	0	0
number of deaths resulting from adverse events	0	0	0	1	1	1	1	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour ulceration
Additional description: Tumour ulceration
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Embolism
Additional description: Embolism
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
General physical health deterioration
Additional description: General physical health deterioration
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
Additional description: Non-cardiac chest pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
Additional description: Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
Additional description: Hypoxia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
Pneumothorax
Additional description: Pneumothorax
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory arrest
Additional description: Respiratory arrest
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory failure
Additional description: Respiratory failure
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Neutrophil count decreased
Additional description: Neutrophil count decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Infusion related reaction
Additional description: Infusion related reaction
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac tamponade
Additional description: Cardiac tamponade
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
Additional description: Pericardial effusion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Haemorrhagic stroke
Additional description: Haemorrhagic stroke
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intracranial haematoma
Additional description: Intracranial haematoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neuropathy peripheral
Additional description: Neuropathy peripheral
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neurotoxicity
Additional description: Neurotoxicity
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Seizure
Additional description: Seizure
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ear and labyrinth disorders
Ear pain
Additional description: Ear pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Keratitis
Additional description: Keratitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
Additional description: Constipation
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
Additional description: Nausea
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
Additional description: Small intestinal obstruction
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
Additional description: Vomiting
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	1 / 1	2 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholangitis
Additional description: Cholangitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
Additional description: Acute kidney injury
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Inappropriate antidiuretic hormone secretion
Additional description: Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Haematoma muscle
Additional description: Haematoma muscle
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Catheter site infection
Additional description: Catheter site infection
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
Additional description: Cellulitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis orbital
Additional description: Cellulitis orbital
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
Additional description: Device related infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Herpes zoster
Additional description: Herpes zoster
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine infection
Additional description: Large intestine infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
Additional description: Sepsis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Septic shock
Additional description: Septic shock
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hypercalcaemia
Additional description: Hypercalcaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypokalaemia
Additional description: Hypokalaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
Additional description: Hyponatraemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Dosing Group 1 (≤ 4 mg/kg (Q3W))	Dosing Group 2 (5 mg/kg (Q3W))	Dosing Group 3 (6 mg/kg (Q3W))	Dosing Group 4 (7 mg/kg (Q3W))	Dosing Group 5 (8 mg/kg (Q3W))	Dosing Group 6 (9 mg/kg (Q3W))	Dosing Group 7 (10 mg/kg (Q3W))	Dosing Group 8 (4 mg/kg (Q2W))	Dosing Group 9 (6 mg/kg (Q2W))
Total subjects affected by non serious adverse events
subjects affected / exposed	19 / 20 (95.00%)	9 / 9 (100.00%)	9 / 9 (100.00%)	12 / 12 (100.00%)	22 / 22 (100.00%)	9 / 9 (100.00%)	8 / 8 (100.00%)	4 / 4 (100.00%)	6 / 6 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma
Additional description: Lipoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Malignant neoplasm progression
Additional description: Malignant neoplasm progression
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Tumour pain
Additional description: Tumour pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	2	0	0	0	1
Vascular disorders
Deep vein thrombosis
Additional description: Deep vein thrombosis
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Flushing
Additional description: Flushing
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Hot flush
Additional description: Hot flush
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Hypertension
Additional description: Hypertension
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	1	0	1	0	0
Hypotension
Additional description: Hypotension
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	1	2	0	0	2	0	0	1	0
Surgical and medical procedures
Tooth extraction
Additional description: Tooth extraction
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
General disorders and administration site conditions
Asthenia
Additional description: Asthenia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	3	5	1	0	0
Chest pain
Additional description: Chest pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Chills
Additional description: Chills
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	2	0	0	0	0	0	0	0	1
Fatigue
Additional description: Fatigue
subjects affected / exposed	7 / 20 (35.00%)	6 / 9 (66.67%)	6 / 9 (66.67%)	7 / 12 (58.33%)	10 / 22 (45.45%)	4 / 9 (44.44%)	2 / 8 (25.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)
occurrences all number	9	8	8	8	15	4	2	2	6
Feeling cold
Additional description: Feeling cold
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0
Gait disturbance
Additional description: Gait disturbance
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	2	0	0	0	0
Infusion site erythema
Additional description: Infusion site erythema
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Infusion site phlebitis
Additional description: Infusion site phlebitis
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Malaise
Additional description: Malaise
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	2	0	0	0	2	0	0	0	1
Mucosal inflammation
Additional description: Mucosal inflammation
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Non-cardiac chest pain
Additional description: Non-cardiac chest pain
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
occurrences all number	1	1	2	0	0	0	0	2	3
Oedema
Additional description: Oedema
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Oedema peripheral
Additional description: Oedema peripheral
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 12 (16.67%)	3 / 22 (13.64%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	2	4	1	0	0	0
Pain
Additional description: Pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0
Peripheral swelling
Additional description: Peripheral swelling
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pyrexia
Additional description: Pyrexia
subjects affected / exposed	2 / 20 (10.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	4 / 12 (33.33%)	2 / 22 (9.09%)	1 / 9 (11.11%)	1 / 8 (12.50%)	3 / 4 (75.00%)	0 / 6 (0.00%)
occurrences all number	3	2	0	5	2	1	2	3	0
Secretion discharge
Additional description: Secretion discharge
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Immune system disorders
Seasonal allergy
Additional description: Seasonal allergy
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
Erectile dysfunction
Additional description: Erectile dysfunction
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Pelvic pain
Additional description: Pelvic pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Vaginal discharge
Additional description: Vaginal discharge
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Vaginal haemorrhage
Additional description: Vaginal haemorrhage
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Vulvovaginal pain
Additional description: Vulvovaginal pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis
Additional description: Allergic bronchitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Aspiration
Additional description: Aspiration
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Cough
Additional description: Cough
subjects affected / exposed	0 / 20 (0.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	0
Dysphonia
Additional description: Dysphonia
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	0	0	0	0	0
Dyspnoea
Additional description: Dyspnoea
subjects affected / exposed	8 / 20 (40.00%)	1 / 9 (11.11%)	2 / 9 (22.22%)	3 / 12 (25.00%)	2 / 22 (9.09%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	10	1	2	6	2	2	0	0	2
Dyspnoea exertional
Additional description: Dyspnoea exertional
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	1	1	0	0
Epistaxis
Additional description: Epistaxis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Haemoptysis
Additional description: Haemoptysis
subjects affected / exposed	1 / 20 (5.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	4	0	0	0	0	0	0	0
Hypoxia
Additional description: Hypoxia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0
Laryngeal oedema
Additional description: Laryngeal oedema
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Oropharyngeal pain
Additional description: Oropharyngeal pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0
Pharyngeal hypoaesthesia
Additional description: Pharyngeal hypoaesthesia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pleural effusion
Additional description: Pleural effusion
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Pulmonary embolism
Additional description: Pulmonary embolism
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	1	0	0	0	1
Pulmonary pain
Additional description: Pulmonary pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Respiratory failure
Additional description: Respiratory failure
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Respiratory tract congestion
Additional description: Respiratory tract congestion
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Sinus congestion
Additional description: Sinus congestion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Tachypnoea
Additional description: Tachypnoea
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Upper-airway cough syndrome
Additional description: Upper-airway cough syndrome
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Wheezing
Additional description: Wheezing
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Psychiatric disorders
Anxiety
Additional description: Anxiety
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	3 / 22 (13.64%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	2	3	0	0	0	1
Confusional state
Additional description: Confusional state
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Depression
Additional description: Depression
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	0	1	0	0	0	0	0
Insomnia
Additional description: Insomnia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	3 / 12 (25.00%)	4 / 22 (18.18%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 4 (25.00%)	2 / 6 (33.33%)
occurrences all number	0	1	1	3	5	1	2	1	4
Investigations
Activated partial thromboplastin time prolonged
Additional description: Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Alanine aminotransferase increased
Additional description: Alanine aminotransferase increased
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	3 / 9 (33.33%)	0 / 12 (0.00%)	7 / 22 (31.82%)	2 / 9 (22.22%)	2 / 8 (25.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	3	9	0	16	2	12	0	3
Ammonia increased
Additional description: Ammonia increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Aspartate aminotransferase increased
Additional description: Aspartate aminotransferase increased
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	3 / 9 (33.33%)	1 / 12 (8.33%)	9 / 22 (40.91%)	2 / 9 (22.22%)	3 / 8 (37.50%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	1	3	8	1	32	2	14	0	6
Blood alkaline phosphatase increased
Additional description: Blood alkaline phosphatase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	2 / 9 (22.22%)	1 / 12 (8.33%)	5 / 22 (22.73%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	1	7	2	0	0	0
Blood calcium increased
Additional description: Blood calcium increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0
Blood creatine increased
Additional description: Blood creatine increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Blood creatinine increased
Additional description: Blood creatinine increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	3 / 9 (33.33%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	3	1	0	0	3	0	0
Blood glucose increased
Additional description: Blood glucose increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Blood iron decreased
Additional description: Blood iron decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Blood lactate dehydrogenase increased
Additional description: Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Blood magnesium increased
Additional description: Blood magnesium increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Blood urea increased
Additional description: Blood urea increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	0
Gamma-glutamyltransferase increased
Additional description: Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0
International normalised ratio increased
Additional description: International normalised ratio increased
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Lymphocyte count decreased
Additional description: Lymphocyte count decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0
Neutrophil count decreased
Additional description: Neutrophil count decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Platelet count decreased
Additional description: Platelet count decreased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	1	1	0	0
Transaminases increased
Additional description: Transaminases increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	2	0	0	1	1
Weight decreased
Additional description: Weight decreased
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	4 / 22 (18.18%)	2 / 9 (22.22%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	1	0	5	2	2	0	0
White blood cell count decreased
Additional description: White blood cell count decreased
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Concussion
Additional description: Concussion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Fall
Additional description: Fall
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	1	0	0	0
Infusion related reaction
Additional description: Infusion related reaction
subjects affected / exposed	4 / 20 (20.00%)	1 / 9 (11.11%)	3 / 9 (33.33%)	2 / 12 (16.67%)	5 / 22 (22.73%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 4 (50.00%)	2 / 6 (33.33%)
occurrences all number	4	1	3	2	5	0	1	2	2
Oral contusion
Additional description: Oral contusion
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Post procedural discomfort
Additional description: Post procedural discomfort
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Cardiac disorders
Atrial fibrillation
Additional description: Atrial fibrillation
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	0	0	0	0	1
Cardiac failure
Additional description: Cardiac failure
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Pericardial effusion
Additional description: Pericardial effusion
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	0	0	0	0	1
Nervous system disorders
Dizziness
Additional description: Dizziness
subjects affected / exposed	3 / 20 (15.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	1	0	2	0	1	0	0
Dysaesthesia
Additional description: Dysaesthesia
subjects affected / exposed	0 / 20 (0.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	0	0	1	0	0
Dysarthria
Additional description: Dysarthria
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Dysgeusia
Additional description: Dysgeusia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	0
Headache
Additional description: Headache
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	1 / 12 (8.33%)	3 / 22 (13.64%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 4 (25.00%)	2 / 6 (33.33%)
occurrences all number	1	2	1	1	3	1	1	1	2
Hypoaesthesia
Additional description: Hypoaesthesia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Lethargy
Additional description: Lethargy
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Memory impairment
Additional description: Memory impairment
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Neuropathy peripheral
Additional description: Neuropathy peripheral
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	2 / 12 (16.67%)	6 / 22 (27.27%)	3 / 9 (33.33%)	0 / 8 (0.00%)	0 / 4 (0.00%)	3 / 6 (50.00%)
occurrences all number	0	1	2	3	8	4	0	0	9
Neurotoxicity
Additional description: Neurotoxicity
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	1	0	0	1	0
Paraesthesia
Additional description: Paraesthesia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	2	0	0	0	0
Peripheral sensory neuropathy
Additional description: Peripheral sensory neuropathy
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	1 / 12 (8.33%)	1 / 22 (4.55%)	2 / 9 (22.22%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	1	2	1	1	3	1	0	1
Seizure
Additional description: Seizure
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Syncope
Additional description: Syncope
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Taste disorder
Additional description: Taste disorder
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0
Tremor
Additional description: Tremor
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
Additional description: Anaemia
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 12 (16.67%)	5 / 22 (22.73%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	6	0	0	6	13	0	0	0	0
Lymph node pain
Additional description: Lymph node pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Neutropenia
Additional description: Neutropenia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	2
Thrombocytopenia
Additional description: Thrombocytopenia
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Ear and labyrinth disorders
Ear disorder
Additional description: Ear disorder
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Ear pain
Additional description: Ear pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0
Tinnitus
Additional description: Tinnitus
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	1	0	0
Eye disorders
Asthenopia
Additional description: Asthenopia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Astigmatism
Additional description: Astigmatism
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Cataract
Additional description: Cataract
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Chalazion
Additional description: Chalazion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Corneal infiltrates
Additional description: Corneal infiltrates
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Corneal toxicity
Additional description: Corneal toxicity
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Dry eye
Additional description: Dry eye
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	0 / 12 (0.00%)	2 / 22 (9.09%)	2 / 9 (22.22%)	0 / 8 (0.00%)	2 / 4 (50.00%)	1 / 6 (16.67%)
occurrences all number	1	1	2	0	3	2	0	2	1
Eye pain
Additional description: Eye pain
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	0	0	2	0	0	0	0
Eyelid ptosis
Additional description: Eyelid ptosis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Glaucoma
Additional description: Glaucoma
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Keratitis
Additional description: Keratitis
subjects affected / exposed	1 / 20 (5.00%)	2 / 9 (22.22%)	2 / 9 (22.22%)	1 / 12 (8.33%)	7 / 22 (31.82%)	2 / 9 (22.22%)	4 / 8 (50.00%)	0 / 4 (0.00%)	4 / 6 (66.67%)
occurrences all number	1	3	2	1	13	8	11	0	16
Keratopathy
Additional description: Keratopathy
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	6	0	0	0	1
Lacrimation increased
Additional description: Lacrimation increased
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Ocular hyperaemia
Additional description: Ocular hyperaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Ocular hypertension
Additional description: Ocular hypertension
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Orbital cyst
Additional description: Orbital cyst
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Photophobia
Additional description: Photophobia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	2	0	0	0	0	1	0	1
Presbyopia
Additional description: Presbyopia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Punctate keratitis
Additional description: Punctate keratitis
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	2	1	0	0	0	0
Pupillary reflex impaired
Additional description: Pupillary reflex impaired
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Retinal degeneration
Additional description: Retinal degeneration
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Retinal detachment
Additional description: Retinal detachment
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Vision blurred
Additional description: Vision blurred
subjects affected / exposed	3 / 20 (15.00%)	2 / 9 (22.22%)	0 / 9 (0.00%)	1 / 12 (8.33%)	4 / 22 (18.18%)	2 / 9 (22.22%)	5 / 8 (62.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	3	2	0	1	5	3	6	0	1
Visual impairment
Additional description: Visual impairment
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
Additional description: Abdominal discomfort
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0
Abdominal distension
Additional description: Abdominal distension
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	1 / 12 (8.33%)	3 / 22 (13.64%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	1	4	0	0	0	0
Abdominal pain
Additional description: Abdominal pain
subjects affected / exposed	3 / 20 (15.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	2 / 12 (16.67%)	5 / 22 (22.73%)	2 / 9 (22.22%)	1 / 8 (12.50%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	4	1	1	2	7	3	2	2	0
Abdominal pain lower
Additional description: Abdominal pain lower
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Abdominal pain upper
Additional description: Abdominal pain upper
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	1	0	0	1	0	0
Aphthous ulcer
Additional description: Aphthous ulcer
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0
Ascites
Additional description: Ascites
subjects affected / exposed	3 / 20 (15.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	0	1	2	0	0	0	0
Constipation
Additional description: Constipation
subjects affected / exposed	5 / 20 (25.00%)	2 / 9 (22.22%)	2 / 9 (22.22%)	4 / 12 (33.33%)	4 / 22 (18.18%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 4 (25.00%)	3 / 6 (50.00%)
occurrences all number	5	2	2	5	5	1	0	1	5
Diarrhoea
Additional description: Diarrhoea
subjects affected / exposed	5 / 20 (25.00%)	1 / 9 (11.11%)	3 / 9 (33.33%)	2 / 12 (16.67%)	7 / 22 (31.82%)	4 / 9 (44.44%)	3 / 8 (37.50%)	2 / 4 (50.00%)	1 / 6 (16.67%)
occurrences all number	6	1	4	2	9	5	3	2	1
Dry mouth
Additional description: Dry mouth
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	1 / 12 (8.33%)	3 / 22 (13.64%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	1	3	1	0	0	0
Dyspepsia
Additional description: Dyspepsia
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	2 / 9 (22.22%)	2 / 8 (25.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	2	0	3	0	0	2	2	0	1
Flatulence
Additional description: Flatulence
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	2
Gastritis
Additional description: Gastritis
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	2	0	0	1	0	0	0	0
Gastrooesophageal reflux disease
Additional description: Gastrooesophageal reflux disease
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Gingival bleeding
Additional description: Gingival bleeding
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Large intestinal obstruction
Additional description: Large intestinal obstruction
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Nausea
Additional description: Nausea
subjects affected / exposed	9 / 20 (45.00%)	2 / 9 (22.22%)	4 / 9 (44.44%)	6 / 12 (50.00%)	10 / 22 (45.45%)	6 / 9 (66.67%)	5 / 8 (62.50%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	14	2	8	7	12	7	6	0	2
Odynophagia
Additional description: Odynophagia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Proctalgia
Additional description: Proctalgia
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Small intestinal obstruction
Additional description: Small intestinal obstruction
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Stomatitis
Additional description: Stomatitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Toothache
Additional description: Toothache
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Upper gastrointestinal haemorrhage
Additional description: Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Vomiting
Additional description: Vomiting
subjects affected / exposed	5 / 20 (25.00%)	2 / 9 (22.22%)	2 / 9 (22.22%)	3 / 12 (25.00%)	6 / 22 (27.27%)	2 / 9 (22.22%)	3 / 8 (37.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	8	4	3	4	9	2	3	0	1
Hepatobiliary disorders
Hyperbilirubinaemia
Additional description: Hyperbilirubinaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Blister
Additional description: Blister
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Dermatitis acneiform
Additional description: Dermatitis acneiform
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Dry skin
Additional description: Dry skin
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0
Ecchymosis
Additional description: Ecchymosis
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Erythema
Additional description: Erythema
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Night sweats
Additional description: Night sweats
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Pruritus
Additional description: Pruritus
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	1	0	2	0	0	0	1
Rash
Additional description: Rash
subjects affected / exposed	3 / 20 (15.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	2 / 22 (9.09%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	3	0	0	1	2	1	0	1	0
Rash maculo-papular
Additional description: Rash maculo-papular
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0	0
Rash papular
Additional description: Rash papular
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0
Rash pruritic
Additional description: Rash pruritic
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0
Skin discolouration
Additional description: Skin discolouration
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Skin exfoliation
Additional description: Skin exfoliation
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Skin mass
Additional description: Skin mass
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Urticaria
Additional description: Urticaria
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Renal and urinary disorders
Acute kidney injury
Additional description: Acute kidney injury
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0
Bladder pain
Additional description: Bladder pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Dysuria
Additional description: Dysuria
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Haematuria
Additional description: Haematuria
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0
Micturition urgency
Additional description: Micturition urgency
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Urinary incontinence
Additional description: Urinary incontinence
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Urinary retention
Additional description: Urinary retention
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Urinary tract pain
Additional description: Urinary tract pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0
Endocrine disorders
Addison's disease
Additional description: Addison's disease
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Hypothyroidism
Additional description: Hypothyroidism
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	1	0	0	0	0	0	1
Inappropriate antidiuretic hormone secretion
Additional description: Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0
Primary adrenal insufficiency
Additional description: Primary adrenal insufficiency
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Arthralgia
Additional description: Arthralgia
subjects affected / exposed	3 / 20 (15.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	3 / 12 (25.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
occurrences all number	3	1	1	7	1	0	0	1	2
Back pain
Additional description: Back pain
subjects affected / exposed	5 / 20 (25.00%)	1 / 9 (11.11%)	3 / 9 (33.33%)	1 / 12 (8.33%)	3 / 22 (13.64%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	6	1	4	1	3	0	1	0	1
Flank pain
Additional description: Flank pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0
Joint stiffness
Additional description: Joint stiffness
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Joint swelling
Additional description: Joint swelling
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Muscle spasms
Additional description: Muscle spasms
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	0	0	1	0	0	0	0
Muscular weakness
Additional description: Muscular weakness
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	0	0	1	0	0	0	0
Musculoskeletal chest pain
Additional description: Musculoskeletal chest pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Musculoskeletal pain
Additional description: Musculoskeletal pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	0	1	0	0	1	1
Myalgia
Additional description: Myalgia
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	2 / 12 (16.67%)	2 / 22 (9.09%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	2	0	0	2	2	0	1	0	4
Myositis
Additional description: Myositis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Neck pain
Additional description: Neck pain
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	1	0	0	0	0	0	0
Pain in extremity
Additional description: Pain in extremity
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	1 / 12 (8.33%)	0 / 22 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 6 (16.67%)
occurrences all number	1	0	2	1	0	4	0	2	1
Pain in jaw
Additional description: Pain in jaw
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Spinal pain
Additional description: Spinal pain
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Infections and infestations
Adenoviral conjunctivitis
Additional description: Adenoviral conjunctivitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0
Candida infection
Additional description: Candida infection
subjects affected / exposed	1 / 20 (5.00%)	1 / 9 (11.11%)	1 / 9 (11.11%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	1	1	0	1	0	0	0	0
Cellulitis
Additional description: Cellulitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Conjunctivitis
Additional description: Conjunctivitis
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0
Lip infection
Additional description: Lip infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0
Ophthalmic herpes zoster
Additional description: Ophthalmic herpes zoster
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Oral infection
Additional description: Oral infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Pneumonia
Additional description: Pneumonia
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Pneumonia viral
Additional description: Pneumonia viral
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Stoma site infection
Additional description: Stoma site infection
subjects affected / exposed	0 / 20 (0.00%)	1 / 9 (11.11%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0
Upper respiratory tract infection
Additional description: Upper respiratory tract infection
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0
Urinary tract infection
Additional description: Urinary tract infection
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	4 / 12 (33.33%)	0 / 22 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	2	0	2	4	0	1	1	0	0
Metabolism and nutrition disorders
Decreased appetite
Additional description: Decreased appetite
subjects affected / exposed	8 / 20 (40.00%)	2 / 9 (22.22%)	4 / 9 (44.44%)	4 / 12 (33.33%)	8 / 22 (36.36%)	5 / 9 (55.56%)	2 / 8 (25.00%)	1 / 4 (25.00%)	0 / 6 (0.00%)
occurrences all number	10	2	5	4	9	5	3	1	0
Dehydration
Additional description: Dehydration
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	1	0	1	1	0	0	1
Fluid overload
Additional description: Fluid overload
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	1
Hypercalcaemia
Additional description: Hypercalcaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	2	0	0	0
Hypercholesterolaemia
Additional description: Hypercholesterolaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0
Hyperglycaemia
Additional description: Hyperglycaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	0	2	0	0	0	1
Hyperkalaemia
Additional description: Hyperkalaemia
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	1	0	0	1	2	0	1	0	1
Hypermagnesaemia
Additional description: Hypermagnesaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	1	0	0
Hypernatraemia
Additional description: Hypernatraemia
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0
Hyperuricaemia
Additional description: Hyperuricaemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	2 / 22 (9.09%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0
Hypoalbuminaemia
Additional description: Hypoalbuminaemia
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	0 / 12 (0.00%)	1 / 22 (4.55%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	1	0	3	0	0	0	0
Hypokalaemia
Additional description: Hypokalaemia
subjects affected / exposed	2 / 20 (10.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	4 / 12 (33.33%)	2 / 22 (9.09%)	4 / 9 (44.44%)	1 / 8 (12.50%)	0 / 4 (0.00%)	2 / 6 (33.33%)
occurrences all number	2	0	1	4	3	4	1	0	2
Hypomagnesaemia
Additional description: Hypomagnesaemia
subjects affected / exposed	3 / 20 (15.00%)	0 / 9 (0.00%)	1 / 9 (11.11%)	2 / 12 (16.67%)	0 / 22 (0.00%)	3 / 9 (33.33%)	2 / 8 (25.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	1	4	0	4	2	0	0
Hyponatraemia
Additional description: Hyponatraemia
subjects affected / exposed	3 / 20 (15.00%)	0 / 9 (0.00%)	3 / 9 (33.33%)	3 / 12 (25.00%)	3 / 22 (13.64%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	3	0	3	3	5	2	0	0	0
Hypophosphataemia
Additional description: Hypophosphataemia
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	1 / 12 (8.33%)	1 / 22 (4.55%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 6 (16.67%)
occurrences all number	0	0	0	2	1	1	0	0	1
Type 2 diabetes mellitus
Additional description: Type 2 diabetes mellitus
subjects affected / exposed	0 / 20 (0.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0
Vitamin D deficiency
Additional description: Vitamin D deficiency
subjects affected / exposed	1 / 20 (5.00%)	0 / 9 (0.00%)	0 / 9 (0.00%)	0 / 12 (0.00%)	0 / 22 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 6 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

15 May 2017

Amendment 1 (version 2) (Global) (15 May 2017) The protocol was revised to: • Update the statistical section for Part B of the study; • Modify the inclusion criteria for subject eligibility; • Add exclusion criteria for advanced or metastatic Stage IV non-small cell lung carcinoma subjects with epidermal growth factor receptor or anaplastic lymphoma kinase genomic alterations; • Update restricted medications section to include cytochrome P450 3A inhibitors and substrates; • Add a section to describe potential important drug-drug interactions; • Add time points for pharmacokinetic assessments.

31 Oct 2017

Amendment 2 (Global) (31 October 2017) The protocol was revised to: • Update the study objectives; • Add a cohort (Part A2) to the study to refine the selection of the recommended Phase 2 dose and update the study design for Part A and Part B to reflect the addition of Part A2; • Update the study design to not allow for over-enrollment in any cohort; • Update the inclusion/exclusion criteria; • Clarify study drug administration; • Update ocular toxicity section to include protective measures for subjects who report ocular symptoms; • Update the use of live vaccines in the excluded medications section to; • Update the dose of glucocorticoids in the restricted medications section; • Update Section 7 to exclude the term pharmacodynamic; • Update module specified events; • Update sample size and statistical analyses

09 Mar 2018

Amendment 3 (Global) (09 March 2018) The protocol was revised to: • Update the study design to allow additional dose levels to be tested in Part A and Part A2 and to include that Germany will only participate in Part B of the study; • Add endometrial carcinoma as a subject’s tumor type to Part A2; • Update the inclusion/exclusion criteria; • Update rationale for dosing section; • Update ocular toxicity section to make protective measures mandatory for subjects who report treatment-emergent ocular symptoms and allow subjects with Grade 2 ocular toxicity to continue treatment upon resolution of symptoms to Grade 1 or baseline; • Clarify exposure in utero and documentation of adverse events by Investigator sections; • Clarify radiology language in the Schedule of Procedures table; and • Update sample size.

10 Sep 2018

Amendment 4 (Global) (10 September 2018) The protocol was revised to: • Include subjects in Part B who have high CD166 expression to ensure the presence of target antigen on tumors which is expected to be necessary for biological activity of CX-2009. • Define CD166 high expression in tumor cells. • Update inclusion criterion for subjects with non-small cell lung cancer in Part B to clarify that subjects must have progressed on anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy. • Clarify recording of adverse events including on-study deaths due to progressive disease. • Update dose management for CX-2009 section to include a process for dose reduction. • Update ocular toxicity section to require mandatory ocular prophylaxis for all subjects being dosed with CX-2009 due to increased rate of ocular toxicity observed at higher dose levels. • Clarify guidelines for CX-2009 dose modifications for Grade 3 treatment-emergent ocular disorders in Table 8. • Clarify that tumor biopsies collected will be fixed and frozen. • Update rapid notification of adverse events of special interest section to include Grade 2 infusion reactions (instead of previously stated Grade 3 and Grade 4) to be reported to the Sponsor or its designee within 24 hours. • Include Appendix I to clarify the process of assessment of CD166 status.

13 Feb 2019

Amendment 5 (Global) (13 February 2019) The protocol was revised to: • Add 2 cohorts (Parts C1 and C2) to the study to allow evaluation of an every 14-day dosing regimen of CX-2009; • Include subjects in the modified toxicity probability interval (mTPI-2) cohort of Part A who have high CD166 expression since preliminary data from this study shows a trend towards activity of CX-2009 in subjects with high CD166 expressing tumors; • Increase the number of subjects in the mTPI-2 cohort of Part A to further refine the recommended Phase 2 dose selection; • Update the inclusion/exclusion criteria to include Parts C1 and C2; • Update ocular toxicity section based on antibody drug conjugate ophthalmology consultant’s guidance on management of N2-deacetyl-N2-(4-mercapto-4-methyl-1-oxopentyl)-maytansine toxin-related ocular toxicities; • Update dose reduction section to include guidance on dose reduction for Parts C1 and C2; and • Update sample size.

09 Aug 2019

Amendment 6 (Global) (09 August 2019) The protocol has been amended to: • Add study Parts D1 and D2 (for a new total of 7 study parts) to evaluate the combination of CX-2009 plus CX-072, with Part D1 comprising dose escalation and Part D2 comprising dose expansion; • Revise eligibility criteria; • Update tumor types eligible for enrollment in Parts B and C2 expansion cohorts to align with new Part D2; • Increase sample size in Part B from up to 14 subjects in each of 7 tumor types (ie, ≤98 subjects) to up to total of 40 subjects in each of 5 tumor types; • For Part C1, add a provision to characterize protease activity in optional pretreatment tumor biopsies; • In Parts C1 and D1, add a specification that prior to dose escalation a minimum of 3 evaluable subjects must be assessed per the modified toxicity interval 2 (mTPI-2) algorithm • Increase sample size in Part C2 from up to 14 subjects in 1 tumor types (ie, ≤14 subjects) to up to total of 40 subjects in each of 5 tumor types; • Add stipulation that dose expansion for monotherapy would occur under Part B or C2; • Add safety stopping rules for the first 6 subjects enrolled in Parts B, C2, and D2 (dose expansion cohorts); • Update clinical experience for CX-2009 and add clinical experience and toxicity management guidelines for CX-072; • Align biopsy collection schedule (optional and mandatory) across all study parts; • Update existing Schedule of Procedures (Appendix B) to incorporate information previously communicated through administrative memos or in accordance with changes made within this amendment; • Update Schedule of Vital Sign Measurements to remove cycle day from table, clarify when height should be collected, and clarify when to measure vital signs in case of an IRR; • Update schedule of pharmacokinetics (PK) and antidrug antibody (ADA) assessment tables

16 Dec 2019

Amendment 6.1 (Global) (16 December 2019) The protocol has been amended to: • Clarify the intention to de-escalate the cohort in Part C1 • Clarify that Parts D1 and D2 will not open for enrollment in UK • Update ocular prophylaxis language to align with published prophylaxis regimen for management of antibody-drug conjugate-induced corneal abnormalities

20 Feb 2020

Amendment 7 (Global) (20 February 2020) The protocol has been amended to: • Update specifications relevant to each section for newly added Parts E1 and E2; • Clarify Part C1 dose de-escalation/escalation based on available safety information; • Clarify Part B – Indication and dose, Part E – Combination of CX-2009 and CX-072 in an every 21-day schedule, Ocular treatment guidelines, Inclusion and exclusion criteria; • Clarify Determination of cluster of differentiation 166 (CD166) expression during the screening period, Biopsy for CD166 determination, Part C1 dose reduction, Part D1 starting dose, Determination of PD-L1 expression for Part D, Co-administration of CX-2009 and CX-072 (Parts D and E)

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
09 Apr 2020	Enrollment into the study was terminated in April 2020 due to a strategic business decision and the Covid Pandemic. The study was terminated by CytomX before patients were enrolled into Parts C2, D1, or D2.	-

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

Additional study parts added in Amendments 5, 6, 6.1, and 7 did not enroll any patients and are not further discussed. Enrollment into the study was terminated in April 2020 and did not complete all planned secondary outcomes.

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Clinical Trial Results:
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)

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Primary: The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy

Primary: The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy

Secondary: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy

Secondary: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy

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Clinical trials

Clinical Trial Results: A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)

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Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy

Primary: The Number of Subjects Experiencing a Dose Limiting Toxicity at Various Dose Levels When Given CX-2009 as a Monotherapy

Secondary: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy

Secondary: The Percentage of Subjects Experiencing Anti-cancer Activity (ORR) at Various Dose Levels When Given CX-2009 as a Monotherapy

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

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Clinical Trial Results:
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)