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Clinical Trial Results:
A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

Summary
EudraCT number	2019-002598-78
Trial protocol	GB
Global end of trial date	11 Apr 2024

Results information
Results version number	v1(current)
This version publication date	27 Apr 2025
First version publication date	27 Apr 2025
Other versions

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

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Trial information

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Sponsor protocol code

ONC001

ISRCTN number

US NCT number

NCT04393298

WHO universal trial number (UTN)

Sponsor organisation name

UCB Biopharma SRL

Sponsor organisation address

Allée de la Recherche 60, Brussels, Belgium, 1070

Public contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com

Scientific contact

Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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

07 Jun 2024

Is this the analysis of the primary completion data?

Yes

Primary completion date

11 Apr 2024

Global end of trial reached?

Yes

Global end of trial date

11 Apr 2024

Was the trial ended prematurely?

Main objective of the trial

Characterize the safety profile of UCB6114

Protection of trial subjects

During the conduct of the study all participants were closely monitored.

Background therapy

Background therapy as permitted in the protocol.

Evidence for comparator

Not applicable

Actual start date of recruitment

09 Jul 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 70

Country: Number of subjects enrolled

United States: 23

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 started to enroll participants in July 2020 and concluded in April 2024.

Screening details

The Participant Flow refers to the Safety Set (SS).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A: Ginisortamab 100 mg

Arm description

Participants received ginisortamab monotherapy 100 milligrams (mg) as an intravenously (iv) infusion every 2 weeks (Q2W) on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 100 mg at pre-specified timepoints.

Part A: Ginisortamab 250 mg

Arm description

Participants received ginisortamab monotherapy 250 mg as an iv infusion Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 250 mg at pre-specified timepoints.

Part A: Ginisortamab 500 mg

Arm description

Participants received ginisortamab monotherapy 500 mg as an iv infusion Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 500 mg at pre-specified timepoints.

Part A: Ginisortamab 1000 mg

Arm description

Participants received ginisortamab monotherapy 1000 mg as an iv infusion Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 1000 mg at pre-specified timepoints.

Part A: Ginisortamab 2000 mg

Arm description

Participants received ginisortamab monotherapy 2000 mg as an iv infusion Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 2000 mg at pre-specified timepoints.

Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D

Arm description

Participants received ginisortamab monotherapy 2000 mg as an iv infusion (60-minute infusion) Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 2000 mg at pre-specified timepoints.

Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D

Arm description

Participants received ginisortamab monotherapy 2000 mg as an iv infusion (30-minute infusion) Q2W on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 2000 mg at pre-specified timepoints.

Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D

Arm description

Participants received ginisortamab monotherapy 3000 mg as an iv infusion (90-minute infusion) every 3 weeks (Q3W) on Day 1 of each 21-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 3000 mg at pre-specified timepoints.

Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D

Arm description

Participants received ginisortamab monotherapy 4000 mg as an iv infusion (120-minute infusion) every 4 weeks (Q4W) on Day 1 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 4000 mg at pre-specified timepoints.

Part B: Ginisortamab 500 mg + TFD/TPI SoC

Arm description

Participants received ginisortamab 500 mg as an iv infusion Q2W in combination with orally administered trifluridine/tipiracil (TFD/TPI) on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 500 mg at pre-specified timepoints.

Part B: Ginisortamab 1000 mg + TFD/TPI SoC

Arm description

Participants received ginisortamab 1000 mg as an iv infusion Q2W in combination with orally administered TFD/TPI on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 1000 mg at pre-specified timepoints.

Part B: Ginisortamab 2000 mg + TFD/TPI SoC

Arm description

Participants received ginisortamab 2000 mg as an iv infusion Q2W in combination with orally administered TFD/TPI on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 2000 mg at pre-specified timepoints.

Part C: Ginisortamab 500 mg + mFOLFOX6 SoC

Arm description

Participants received ginisortamab 500 mg as an iv infusion Q2W in combination with mFOLFOX6 chemotherapy (oxaliplatin, leucovorin, and 5-fluorouracil) on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 500 mg at pre-specified timepoints.

Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC

Arm description

Participants received ginisortamab 1000 mg as an iv infusion Q2W in combination with mFOLFOX6 chemotherapy (oxaliplatin, leucovorin, and 5-fluorouracil) on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 1000 mg at pre-specified timepoints.

Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC

Arm description

Participants received ginisortamab 2000 mg as an iv infusion Q2W in combination with mFOLFOX6 chemotherapy (oxaliplatin, leucovorin, and 5-fluorouracil) on Day 1 and Day 15 of each 28-day treatment cycle until the occurrence of progressive disease, unacceptable toxicity, or participant withdrawal.

Arm type

Experimental

Investigational medicinal product name

Ginisortamab

Investigational medicinal product code

Other name

UCB6114

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Participants received Ginisortamab 2000 mg at pre-specified timepoints.

Number of subjects in period 1	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC
Started	3	5	5	6	6	8	8	8	8	9	4	8	5	3	7
Completed	1	1	2	3	3	1	4	5	2	5	3	3	3	2	0
Not completed	2	4	3	3	3	7	4	3	6	4	1	5	2	1	7
Clinical Progression: Not suitable for SFU return	-	-	-	-	-	1	-	-	-	-	-	-	-	-	1
Adverse event, serious fatal	-	-	-	-	-	1	1	-	1	1	-	1	1	-	1
Started a New Cancer Treatment	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-
Due to symptoms (New Brain Metastases)	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Symptomatic Cancer - Unfit to take a call	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-
Consent withdrawn by participant, not due to AE	-	-	1	-	-	-	-	-	-	-	-	-	-	-	3
Passed Away on The 30 Oct 2020	1	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Since no Treatment Administered at Cycle 2 Day 15	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-
Disease Progression Confirmed by Scans (CT/MRI)	-	1	-	-	-	-	-	-	-	-	-	-	-	-	-
Disease Progression	-	1	-	-	-	3	2	1	2	1	-	3	-	-	1
Further Deterioration Noted at Clinic review	-	-	1	-	-	-	-	-	-	-	-	-	-	-	-
Adverse event, non-fatal	-	-	-	-	1	-	-	-	2	-	-	-	1	1	-
Progressive Disease and Subsequent Death	-	-	-	-	-	-	1	-	-	-	-	-	-	-	-
Patient Passed Away	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-
Clinical Progression in Combination with AE	-	-	-	-	-	-	-	-	-	1	-	-	-	-	-
Progressive Disease (PD)	-	-	-	3	-	-	-	-	-	-	-	-	-	-	-
Progression	1	-	-	-	-	-	-	-	-	-	1	1	-	-	-
Progressive Disease - New Brain Mets on CT Head	-	-	-	-	-	1	-	-	-	-	-	-	-	-	-
Patient Discharged to Hospice	-	-	-	-	-	-	-	-	1	-	-	-	-	-	-
Clinical Progression	-	2	-	-	-	-	-	-	-	-	-	-	-	-	-
Sponsor decision- sepsis (treatment delay)	-	-	-	-	1	-	-	-	-	-	-	-	-	-	-
Patient Deceased	-	-	-	-	-	-	-	1	-	-	-	-	-	-	-
Lack of efficacy	-	-	-	-	-	-	-	-	-	-	-	-	-	-	1

Baseline characteristics

Top of page

Reporting group title

Part A: Ginisortamab 100 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 250 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 500 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 1000 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 2000 mg

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D

Reporting group description

Reporting group title

Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D

Reporting group description

Reporting group title

Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D

Reporting group description

Reporting group title

Part B: Ginisortamab 500 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 1000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 2000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 500 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC

Reporting group description

Reporting group values	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC	Total
Number of subjects	3	5	5	6	6	8	8	8	8	9	4	8	5	3	7	93
Age Categorical
Units: participants
18 - <65 years	1	4	3	3	3	7	3	5	4	7	4	7	3	2	5	61
65 - <85 years	2	1	2	3	3	1	5	3	4	2	0	1	2	1	2	32
Age Continuous
Units: Years
arithmetic mean (standard deviation)	65.0 ( 1.0 )	54.4 ( 11.0 )	58.2 ( 12.2 )	65.3 ( 8.0 )	60.7 ( 9.5 )	56.6 ( 12.0 )	67.3 ( 6.3 )	60.9 ( 6.7 )	60.8 ( 17.6 )	57.6 ( 9.5 )	51.5 ( 6.2 )	57.6 ( 14.2 )	58.6 ( 10.7 )	63.0 ( 13.0 )	61.1 ( 9.1 )	-
Sex: Female, Male
Units: participants
Female	0	2	3	2	1	3	3	5	2	4	2	2	2	1	3	35
Male	3	3	2	4	5	5	5	3	6	5	2	6	3	2	4	58

End points

Top of page

Reporting group title

Part A: Ginisortamab 100 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 250 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 500 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 1000 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 2000 mg

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D

Reporting group description

Reporting group title

Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D

Reporting group description

Reporting group title

Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D

Reporting group description

Reporting group title

Part B: Ginisortamab 500 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 1000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 2000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 500 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC

Reporting group description

Primary: Percentage of Participants with treatment-emergent adverse events (TEAEs)

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End point title

Percentage of Participants with treatment-emergent adverse events (TEAEs) ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date on or after the first dose of UCB6114 up until the last dose of Ginisortamab (UCB6114) +30 days (i.e. up to 3.8 years). The SS consisted of all study participants who received at least 1 full or partial dose of Ginisortamab (UCB6114).

End point type

Primary

End point timeframe

From Baseline until the End of Study (up to 3.8 years)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC
Number of subjects analysed	3	5	5	6	6	8	8	8	8	9	4	8	5	3	7
Units: percentage of participants
number (not applicable)	100	100	100	100	100	87.5	100	87.5	100	100	100	100	100	100	100

No statistical analyses for this end point

Primary: Percentage of participants based on severity of treatment-emergent adverse events

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End point title

Percentage of participants based on severity of treatment-emergent adverse events ^[2]

End point description

AE is any untoward medical occurrence in patient or clinical study participant, temporally associated with use of study medication, whether or not considered related to study medication. AE can therefore be any unfavorable and unintended sign(abnormal laboratory finding), symptom, or disease(new or exacerbated) temporally associated with use of study medication. TEAE: any AE with start date on or after first dose of UCB6114 up until last dose of Ginisortamab(UCB6114)+30 days. Event for which no Common Terminology Criteria for AE(CTCAE) severity grade was recorded by investigator but intensity was recorded instead was assigned as follows to CTCAE severity grade:Severe=Grade 3, Life Threatening (indicated on electronic case report form (eCRF) for event that is serious)=Grade 4, Death (indicated on the eCRF for event that is serious or has outcome of death)=Grade 5. As planned, data reported for National Cancer Institute (NCI) CTCAE grade >=3 TEAEs and related TEAEs. Safety set.

End point type

Primary

End point timeframe

From Baseline until the End of Study (up to 3.8 years)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC
Number of subjects analysed	3	5	5	6	6	8	8	8	8	9	4	8	5	3	7
Units: percentage of participants
number (not applicable)
NCI CTCAE grade >=3 TEAEs	66.7	40.0	40.0	0	50.0	62.5	50.0	37.5	62.5	55.6	75.0	87.5	100	100	85.7
NCI CTCAE grade >=3 related TEAEs	0	0	0	0	0	0	0	0	12.5	22.2	0	25.0	40.0	0	14.3

No statistical analyses for this end point

Primary: Number of Participants with dose-limiting toxicities (DLTs)

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End point title

Number of Participants with dose-limiting toxicities (DLTs) ^[3]

End point description

DLT:any AE at least related to study medication that occurs during Cycle 1 and met following criteria:Grade (Gr) 3 or 4 nonhematological toxicity according to NCI CTCAE(Version 5.0) except for alopecia, or nausea, vomiting, or diarrhea that reverses to Gr ≤2 within 24 hours (hr) with appropriate medical therapy; Gr 3 or 4 biochemical abnormality that persists despite maximal supportive treatment or biochemical abnormalities that is symptomatic and nontransient; Any Gr ≥3 hematological toxicity of >5 days duration or febrile neutropenia (absolute neutrophil count [ANC]<1000/cubic millimeter[mm3] with single temperature of >38.3°C or sustained temperature ≥38°C for more than one hr), infection with Gr 3 or 4 neutropenia, thrombocytopenia with bleeding or requiring platelet transfusion, or Gr 4 thrombocytopenia; Prolonged Gr 2 diarrhea(>7 days) despite adequate antidiarrheal medication, or multiple Grade 1or 2 toxicities (eg, Gr 1 or 2 diarrhea, vomiting, rash, and fatigue). Safety set.

End point type

Primary

End point timeframe

From Baseline throughout 28 days (Cycle 1)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical hypothesis testing was planned for this study. Results were summarized as descriptive statistics only.

End point values	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC
Number of subjects analysed	3	5	5	6	6	8	8	8	8	9	4	8	5	3	7
Units: participants	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0

No statistical analyses for this end point

Secondary: Part A and A1: UCB6114 Serum concentration by scheduled assessment and cohort

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End point title

Part A and A1: UCB6114 Serum concentration by scheduled assessment and cohort ^[4]

End point description

Blood samples for ginisortamab serum concentration analysis were collected at different timepoints following the first dose of ginisortamab. The data is reported for Part A and A1. Pharmacokinetic Set (PKS) included all study participants in SS (all study participants who received at least 1 full or partial dose of Ginisortamab [UCB6114]) who had at least 1 evaluable PKS concentration (ie, a sample which is above the lower limit of quantitation [0.02μg/mL] and for which the date and time of the sample and prior date and time of dosing are known). Here, “n” signifies participants who were evaluable at specified time points. 9999: GeoMean and GeoCV (%) were only calculated if at least 2/3 of the concentrations are quantified at the respective timepoint. 99999: As per-specified in the SAP and protocol, analysis was not planned at this timepoint. Therefore, data was not collected and reported.

End point type

Secondary

End point timeframe

Parts A: Cycle 1 (Day 1 end of infusion [EOI] and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose); Part A 1: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose)

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: UCB6114 Serum concentration for Part B and C arms are reported in the separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 500 mg	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D
Number of subjects analysed	3	5	5	6	6	8	8	8	8
Units: microgram per milliliter (ug/mL)
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 EOI (n=3,5,4,5,6,8,8,8,5)	18.0477 ( 10.0206 )	72.5261 ( 24.1924 )	130.7757 ( 14.1088 )	277.5536 ( 10.8287 )	552.3530 ( 19.5548 )	592.2331 ( 26.1556 )	593.1846 ( 22.2154 )	946.0883 ( 19.3798 )	1357.6103 ( 20.4135 )
Cycle 1 Day 15 Predose (n=3,5,5,6,5,7,8,8,8)	4.4210 ( 10.1288 )	12.8115 ( 27.1385 )	24.3743 ( 31.2011 )	61.4527 ( 33.1491 )	92.0396 ( 38.4595 )	105.5277 ( 25.1756 )	97.1957 ( 39.3439 )	99999 ( 99999 )	99999 ( 99999 )
Cycle 2 Day 1 Predose (n=2,1,5,6,4,4,8,6,7)	9999 ( 9999 )	9999 ( 9999 )	34.6409 ( 26.9986 )	67.0799 ( 37.9557 )	149.3886 ( 37.0769 )	193.4242 ( 34.5942 )	147.2154 ( 26.4979 )	124.7274 ( 44.3198 )	98.9331 ( 33.8567 )
Cycle 2 Day 15 Predose (n=1,1,4,5,4,8,8,8,8)	9999 ( 9999 )	9999 ( 9999 )	42.6861 ( 38.1929 )	78.2336 ( 35.0467 )	166.4011 ( 34.1041 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Part B and C: UCB6114 concentration by scheduled assessment and dose level

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End point title

Part B and C: UCB6114 concentration by scheduled assessment and dose level ^[5]

End point description

Blood samples for ginisortamab serum concentration analysis were collected at timepoints following the (Cycle 1 Day 1) and the (Cycle 2 Day 1) administration of ginisortamab. Data is reported for Part B and Part C. The PKS included all study participants in the SS (all study participants who received at least 1 full or partial dose of Ginisortamab [UCB6114]) who had at least 1 evaluable PKS concentration (ie, a sample which is above the lower limit of quantitation [0.02μg/mL] and for which the date and time of the sample and prior date and time of dosing are known). Here, “n” signifies participants who were evaluable at specified time points. Here, “99999” signifies GeoMean and GeoCV (%) were only calculated if at least 2/3 of the concentrations are quantified at the respective timepoint.

End point type

Secondary

End point timeframe

Parts B and C: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose)

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: UCB6114 Serum concentration for Part A and A1 arms are reported in the separate endpoint. Therefore, no data was reported for these arms in this endpoint.

End point values	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC
Number of subjects analysed	9	4	8	5	3	7
Units: ug/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 EOI (n=7,4,7,5,3,7)	104.0606 ( 15.3565 )	250.8708 ( 7.6032 )	463.5265 ( 28.6333 )	122.8221 ( 14.8778 )	175.0745 ( 34.7390 )	471.9576 ( 17.1727 )
Cycle 1 Day 15 Predose (n=8,3,7,5,3,7)	19.7473 ( 42.6072 )	37.4171 ( 14.8496 )	83.4236 ( 30.8533 )	16.8917 ( 33.2664 )	32.3094 ( 56.2327 )	70.7026 ( 50.9842 )
Cycle 2 Day 1 Predose (6,3,6,5,3,5)	33.0061 ( 35.3957 )	61.0398 ( 5.0117 )	118.0926 ( 29.3051 )	25.4863 ( 53.6347 )	82.7657 ( 47.9648 )	141.6084 ( 30.8310 )
Cycle 2 Day 15 Predose (n=6,4,5,3,2,3)	38.3595 ( 42.1013 )	55.0249 ( 39.4082 )	135.5849 ( 32.8644 )	24.7120 ( 83.6183 )	99999 ( 99999 )	135.0042 ( 43.8716 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From Baseline up to End of the Study (up to 3.8 years)

Adverse event reporting additional description

A TEAE was defined as any AE with a start date on or after the first dose of UCB6114 until the last dose of Ginisortamab (UCB6114) +30 days. A pre-treatment AE which increased in severity on or after the first dose of study treatment was also counted as a TEAE. Analysis set: safety set.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

26.1

Reporting group title

Part A: Ginisortamab 250 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 100 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 2000 mg

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D

Reporting group description

Reporting group title

Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D

Reporting group description

Reporting group title

Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D

Reporting group description

Reporting group title

Part B: Ginisortamab 500 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 1000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part B: Ginisortamab 2000 mg + TFD/TPI SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 500 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC

Reporting group description

Reporting group title

Part A: Ginisortamab 1000 mg

Reporting group description

Reporting group title

Part A: Ginisortamab 500 mg

Reporting group description

Reporting group title

Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D

Reporting group description

Part A: Ginisortamab 250 mg

Part A: Ginisortamab 100 mg

Part A: Ginisortamab 2000 mg

Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D

Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D

Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC

Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D

Part B: Ginisortamab 500 mg + TFD/TPI SoC

Part B: Ginisortamab 1000 mg + TFD/TPI SoC

Part B: Ginisortamab 2000 mg + TFD/TPI SoC

Part C: Ginisortamab 500 mg + mFOLFOX6 SoC

Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC

Part A: Ginisortamab 1000 mg

Part A: Ginisortamab 500 mg

Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 5 (60.00%)

2 / 3 (66.67%)

1 / 6 (16.67%)

1 / 8 (12.50%)

2 / 8 (25.00%)

2 / 7 (28.57%)

5 / 8 (62.50%)

4 / 9 (44.44%)

2 / 4 (50.00%)

4 / 8 (50.00%)

5 / 5 (100.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

1 / 5 (20.00%)

2 / 8 (25.00%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Cancer pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Embolism

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Catheter site thrombosis

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

2 / 5 (40.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary hypertension

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary oedema

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 8 (12.50%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Overdose

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Toxicity to various agents

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Humerus fracture

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infusion related reaction

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Myocardial infarction

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Cerebrovascular accident

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain upper

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Large intestine perforation

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Large intestinal obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 8 (12.50%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Abdominal pain lower

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

1 / 4 (25.00%)

1 / 8 (12.50%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Mallory-Weiss syndrome

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biliary obstruction

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

1 / 4 (25.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Urogenital fistula

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Acute kidney injury

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Musculoskeletal and connective tissue disorders

Musculoskeletal pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sacral pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

Lower respiratory tract infection bacterial

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Peritonitis bacterial

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Liver abscess

subjects affected / exposed

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Sepsis

subjects affected / exposed

1 / 5 (20.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

1 / 7 (14.29%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular device infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

1 / 8 (12.50%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 9 (0.00%)

0 / 4 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Lower respiratory tract infection

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Neutropenic sepsis

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

1 / 8 (12.50%)

1 / 5 (20.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 3

0 / 0

1 / 3

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Staphylococcal bacteraemia

subjects affected / exposed

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 8 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

1 / 9 (11.11%)

0 / 4 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 8 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Part A: Ginisortamab 250 mg	Part A: Ginisortamab 100 mg	Part A: Ginisortamab 2000 mg	Part A1: Ginisortamab 2000 mg Q2W (60-min), 28D	Part A1: Ginisortamab 2000 mg Q2W (30-min), 28D	Part C: Ginisortamab 2000 mg + mFOLFOX6 SoC	Part A1: Ginisortamab 4000 mg Q4W (120-min), 28D	Part B: Ginisortamab 500 mg + TFD/TPI SoC	Part B: Ginisortamab 1000 mg + TFD/TPI SoC	Part B: Ginisortamab 2000 mg + TFD/TPI SoC	Part C: Ginisortamab 500 mg + mFOLFOX6 SoC	Part C: Ginisortamab 1000 mg + mFOLFOX6 SoC	Part A: Ginisortamab 1000 mg	Part A: Ginisortamab 500 mg	Part A1: Ginisortamab 3000 mg Q3W (90-min), 21D
Total subjects affected by non serious adverse events
subjects affected / exposed	5 / 5 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	7 / 8 (87.50%)	8 / 8 (100.00%)	7 / 7 (100.00%)	8 / 8 (100.00%)	9 / 9 (100.00%)	4 / 4 (100.00%)	8 / 8 (100.00%)	5 / 5 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	7 / 8 (87.50%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0	0
Embolism
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vena cava thrombosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hypertension
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	1	0	0	0
Hypotension
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	1	1	0	0	0	0	0
Chills
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Fatigue
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	3 / 8 (37.50%)	5 / 8 (62.50%)	5 / 7 (71.43%)	3 / 8 (37.50%)	5 / 9 (55.56%)	2 / 4 (50.00%)	2 / 8 (25.00%)	2 / 5 (40.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	3 / 5 (60.00%)	0 / 8 (0.00%)
occurrences all number	1	2	4	4	6	6	3	8	2	3	3	2	8	3	0
Feeling cold
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Mucosal inflammation
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	1	1	1	1	0	0	0
Oedema peripheral
subjects affected / exposed	0 / 5 (0.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	2	2	0	1	1	0	1	0	0	1	0	0	0	1
Pyrexia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	3 / 9 (33.33%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 8 (25.00%)
occurrences all number	0	0	0	0	2	0	1	3	0	0	0	1	0	0	2
Peripheral swelling
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Prostatitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Pruritus genital
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Aspiration
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Cough
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	3 / 5 (60.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	1	0	1	0	1	0	1	3	2	0	1	0
Dyspnoea
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	1	0	0	0	0	0	1	0	0	2	0	1	0	1
Dyspnoea exertional
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	1	1	0	0	0	0	2	1	0	1	0
Hypoxia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Haemoptysis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0
Rhinorrhoea
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pleural effusion
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 8 (12.50%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Oropharyngeal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Psychiatric disorders
Depressed mood
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Confusional state
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Anxiety
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Depression
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Insomnia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hallucination, auditory
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	3 / 8 (37.50%)	0 / 7 (0.00%)	1 / 8 (12.50%)	2 / 9 (22.22%)	2 / 4 (50.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	1	3	0	1	2	3	1	2	0	1	0	0
Amylase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Aspartate aminotransferase
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 8 (12.50%)	3 / 8 (37.50%)	0 / 7 (0.00%)	2 / 8 (25.00%)	3 / 9 (33.33%)	2 / 4 (50.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	1 / 5 (20.00%)	1 / 8 (12.50%)
occurrences all number	1	0	2	1	3	0	2	3	4	1	2	1	2	2	1
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	2 / 8 (25.00%)	1 / 7 (14.29%)	2 / 8 (25.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	2	1	2	1	2	1	5	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	3 / 9 (33.33%)	2 / 4 (50.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	0	0	1	0	0	4	4	0	1	0	0	0	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Blood triglycerides increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Blood creatinine increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	0	0	2	0	0	1	0
C-reactive protein increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	1 / 9 (11.11%)	2 / 4 (50.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	1	0	2	0	2	1	5	1	4	0	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	1	0	0	0	0	0
Electrocardiogram T wave amplitude decreased
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	3 / 7 (42.86%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 4 (0.00%)	4 / 8 (50.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	4	0	4	0	7	1	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	3	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	2 / 8 (25.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	2	0	2	2	2	1	0	0	0	0
Prothrombin time prolonged
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	2 / 7 (28.57%)	2 / 8 (25.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	2	2	2	0	0	0	0	1	1	0
White blood cell count decreased
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	5 / 8 (62.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	11	2	0	0	0	0
Lipase increased
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	1	0	1	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Craniofacial fracture
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Infusion related reaction
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	1	2	0	0	0	0
Fall
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Humerus fracture
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	1	1	0
Arrhythmia supraventricular
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Balance disorder
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Brain oedema
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Cold dysaesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	1	0	0	0	2	1	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	3	0	0	0	0	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Lethargy
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	2 / 9 (22.22%)	1 / 4 (25.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	2	1	3	1	1	2	0	1	0	0
Hypoaesthesia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	1	0	1	0	1	0	0	0	1	0
Neurotoxicity
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	6	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	3	0	0	0
Parosmia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Syncope
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0
Blood and lymphatic system disorders
Lymphopenia
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	3	0	0	0	0	0	0
Leukocytosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Anaemia
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	1 / 8 (12.50%)	2 / 7 (28.57%)	2 / 8 (25.00%)	5 / 9 (55.56%)	1 / 4 (25.00%)	6 / 8 (75.00%)	3 / 5 (60.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	1	0	2	1	1	4	5	12	2	14	11	5	1	0	2
Neutropenia
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	5 / 9 (55.56%)	3 / 4 (75.00%)	3 / 8 (37.50%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	2	0	0	0	3	0	14	17	8	1	3	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	2 / 9 (22.22%)	1 / 4 (25.00%)	2 / 8 (25.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	2	0	3	1	2	3	1	0	0	0
Eye disorders
Dry eye
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Eye pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	1	0	2	0	0	0	0
Abdominal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	3 / 7 (42.86%)	2 / 8 (25.00%)	2 / 9 (22.22%)	2 / 4 (50.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	4	1	0	3	3	2	4	1	2	0	0	0	1
Abdominal pain upper
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 8 (25.00%)
occurrences all number	1	0	0	1	0	0	1	2	0	0	0	0	0	0	2
Abnormal faeces
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Aorto-oesophageal fistula
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Ascites
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Constipation
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	2 / 7 (28.57%)	0 / 8 (0.00%)	2 / 9 (22.22%)	1 / 4 (25.00%)	4 / 8 (50.00%)	3 / 5 (60.00%)	2 / 3 (66.67%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 8 (12.50%)
occurrences all number	0	0	2	1	0	2	0	3	1	4	3	2	1	1	1
Diarrhoea
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	4 / 6 (66.67%)	0 / 8 (0.00%)	2 / 8 (25.00%)	2 / 7 (28.57%)	1 / 8 (12.50%)	3 / 9 (33.33%)	2 / 4 (50.00%)	2 / 8 (25.00%)	3 / 5 (60.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	7	0	4	2	1	6	2	2	4	3	0	0	0
Dry mouth
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0
Dysphagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	2 / 5 (40.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	5	0	0	0	0
Epigastric discomfort
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Eructation
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Food poisoning
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	1	1	0
Oesophageal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Obstruction gastric
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Nausea
subjects affected / exposed	2 / 5 (40.00%)	1 / 3 (33.33%)	4 / 6 (66.67%)	1 / 8 (12.50%)	2 / 8 (25.00%)	4 / 7 (57.14%)	1 / 8 (12.50%)	6 / 9 (66.67%)	2 / 4 (50.00%)	4 / 8 (50.00%)	5 / 5 (100.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	2 / 8 (25.00%)
occurrences all number	2	2	4	1	3	4	2	12	3	6	5	0	3	2	3
Mouth ulceration
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2	0	0	0	0
Oesophageal stenosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Melaena
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	2 / 3 (66.67%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	2	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vomiting
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	0 / 8 (0.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	5 / 9 (55.56%)	2 / 4 (50.00%)	1 / 8 (12.50%)	4 / 5 (80.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	1	2	0	3	1	1	6	2	1	7	0	1	1	0
Hepatobiliary disorders
Hepatomegaly
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Portal vein thrombosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Hypertransaminasaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	2	0	0	0	0	0
Dermatitis diaper
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Erythema
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	1	1	0	1	0	0	0	0	0
Rash
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0
Urticaria
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Rash papular
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Chromaturia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Acute kidney injury
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hydroureter
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	1	0	0	0	0
Pollakiuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Proteinuria
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	2 / 4 (50.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	0	0	2	2	1	0	0	0	0	0
Back pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	2 / 8 (25.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	1 / 3 (33.33%)	3 / 6 (50.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	2	1	0	0	0	2	3	2	4	1	0
Bone pain
subjects affected / exposed	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Flank pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Musculoskeletal chest pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Limb discomfort
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	1	2	0	0	1	0	0	0	0
Osteoporosis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pathological fracture
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Synovial cyst
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Infections and infestations
Abdominal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	0	0	0	2	1	0	1	1	1	1	1
Cellulitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Candida infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	1 / 4 (25.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	1	0	0	0	2	1	0	1	0	1	0	0
Oral candidiasis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0	0	1	0	0	0	0
Pneumonia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Sinusitis bacterial
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	1 / 4 (25.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	1 / 8 (12.50%)	1 / 9 (11.11%)	1 / 4 (25.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	1	2	1	1	2	1	1	0	0	2	0
Urosepsis
subjects affected / exposed	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	0	0
Vaginal infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vascular device infection
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 5 (20.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	1 / 8 (12.50%)	0 / 8 (0.00%)	5 / 7 (71.43%)	2 / 8 (25.00%)	6 / 9 (66.67%)	0 / 4 (0.00%)	3 / 8 (37.50%)	3 / 5 (60.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	0 / 8 (0.00%)
occurrences all number	1	1	2	1	0	5	2	7	0	3	3	0	1	1	0
Dehydration
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	0	1	0	0	1
Hypercalcaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	2 / 9 (22.22%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 8 (12.50%)	0 / 8 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	1	0	0	1	1	0	0	2	0	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	1	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 9 (11.11%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 8 (12.50%)
occurrences all number	0	0	0	0	2	0	1	0	0	1	1	0	0	0	1
Hypophagia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hypophosphataemia
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	1	0	0	0	0	0
Iron deficiency
subjects affected / exposed	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 8 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 9 (0.00%)	0 / 4 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 8 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

11 Jun 2020

Protocol Amendment 1 was dated 11-Jun-2020: - Sponsor name was updated. - Number of participants statement updated. - Timing of SFU visit updated and allowance for Final Visit was conducted by phone. - Footnote to the schema was updated. - Cycle 2 Day 2 column and Cycle 3 onwards Day 8 column deleted as all assessments on those days was deleted. - Blood collection for PK analysis row – samples deleted from Cycle 2 Day 2 and Final Visit. - Blood collection immunogenicity (ADA) row – samples deleted from Cycle 2 Day 15, Cycle 3 onwards Day 15, and Final Visit. - Added new row for blood collection for circulating tumor deoxyribonucleic acid (ctDNA) analysis. - Added new row for survival census. - Added new row for coagulation. - Footnote a was corrected to delete reference to Day 2 of Cycle 2. - Footnote was deleted. - Footnote was corrected to delete reference to Day 8 of Cycle 3 and Cycle 4 onwards. - Footnote was added to the headings for columns Cycle 1 (Days 1 and 15), Cycle 2 (Day 15), and Cycle 3 onwards (Days 1 and 15) to specify timing of predose and postdose safety assessments at these visits. - Footnote was revised to include coagulation. - Footnote was revised to specify timing of electrocardiogram (ECG) assessments due to reduction in number of assessments. - Footnote was revised to clarify use of urine vs serum pregnancy assessments. -Footnote was revised to correct a grammatical error. - Footnote was added to the Cycle 1 Day 1 for the urinalysis, hematology, blood chemistry, and coagulation rows. - Footnote was revised to add coagulation, Clarification of timing of Day 1 predose sample collection was added. Clarified that laboratory tests may be obtained 24h prior to the scheduled visit. - Footnote was revised to specify timing of vital sign assessments on Cycle 1 Day 1. - Footnote was revised to specify types of urine abnormalities that require microscopic analysis. - Footnote was revised to specify collection windows for end of infusion samples.

11 Jun 2020

Protocol Amendment 1 was dated 11-Jun-2020: - Footnote was revised to clarify collection of antidrug antibody (ADA) samples. -Footnote was revised to add use of samples for assay verification. - Footnote was revised to clarify timing of tumor assessments prior to starting study medication and to specify exception for prior computed tomography (CT) or magnetic resonance imaging (MRI) scan. - Footnote was added to specify which procedures were assessed Day 15 only of Cycle 1. - Footnote was added to specify timing of ctDNA sampling on Cycle 3 onwards Day 1. - Footnote was added to specify that echocardiograms were only be assessed at evennumbered cycles from Cycle 3 onwards. - Footnote was added to clarify requirements for tumor assessments at Safety Follow-Up (SFU) visit. - Footnote was added to clarify when tumor assessment is not required at SFU Visit. - Footnote was added to specify predose eligibility assessment at Cycle 1 Day 1. - Footnote was added to clarify liver laboratory assessments in the case of bone metastases. - Footnote was added to specify completion of survival census. - Footnote was added to clarify timing of complete and symptom-directed physical examinations. - Row for Part B: colorectal carcinoma changed to colorectal adenocarcinoma. - Sentence “Higher or lower doses may be considered based on emerging data.” was deleted. - Pancreatic carcinoma changed to pancreatic adenocarcinoma. - Specified 16-day observation for participants who enroll after sentinel participant experiences a dose limiting toxicity (DLT). - Clarification of design choices with expanded explanatory text. - Clarified Safety Monitoring Committee (SMC) role in dose decisions and role in adding additional dose levels. Clarified that doses above 2000mg require an amendment. - Row Part A: Term pancreatic carcinoma corrected to term pancreatic adenocarcinoma Rows Part B, Part D, and Part F: Term colorectal carcinoma corrected to colorectal adenocarcinoma.

11 Jun 2020

Protocol Amendment 1 was dated 11-Jun-2020: - Inclusion criterion was renumbered; terms pancreatic carcinoma and colorectal carcinoma corrected pancreatic adenocarcinoma and colorectal adenocarcinoma, respectively. - Inclusion criterion was renumbered and was changed from “or” to “and”. - Exclusion criterion was deleted. Exclusion criterion was renumbered; and was modified to add history of biliary stent. - Exclusion criterion was renumbered and was modified to remove “or any other type of medical research”. - New criterion: Exclusion criterion was added to specify criterion for renal function. - New criterion: Exclusion criterion was added to exclude major surgery prior to study drug initiation. - New criterion: Exclusion criterion was added to specify criteria for coagulation parameters. - Drug accountability procedure changed to use of drug accountability logs instead of electronic case report form (eCRF). - Term “concomitant” was deleted from (redundant with sentence preceding bulleted list) - Footnote was changed to spell out pharmacokinetics (PK) terms. - List of abbreviations for table was updated. - Footnote was deleted as any doses higher than 2000mg would be subject to a substantial protocol amendment. - Text was added to specify the maximum amount of blood collected from participants during each part of the study. - Coagulation added to sample types; number and volumes of samples updated, total blood volumes updated. - Clarified timing of complete and symptomdirected physical examinations. Clarified that height were only be recorded at Screening. - Coagulation added to types of laboratory assessments. - Text was updated to reflect use of serum or urine pregnancy tests. - AUCtau changed to AUC0-336h. - Footnote was updated to reflect reporting. - Deleted PK sample collection from Final Visit.

11 Jun 2020

Protocol Amendment 1 was dated 11-Jun-2020:- Cycle 1, Day 15 (samples 9 and 10), Day 16 (sample 11), and Day 22 (sample 12) sampling times and predose/postdose timepoints updated. - Cycle 2, Day 1 (samples 13, 14, and 15) sampling times and predose/postdose timepoints updated. - First note in footnotes updated to reflect number of samples and blood volumes. - New note added to footnotes to specify predose sample summarization in statistical analysis. - Footnote added to specify collection of Cycle 3 Day 1 PK sample in subjects who were not continuing treatment. - Specified exception for prior CT or MRI scan. Moved tumor assessments from Final Visit to SFU visit. - Blood volumes updated. - New section added. - Blood volume corrected. - Sentence regarding laboratory manual deleted. - Text updated to reflect reduction in total number of samples taken during Cycles 2, 3, and 4. - Blood sample timepoints for ADA analysis: Deletion of Day 15 samples for Cycles 2, 3, and 4. Clarification of timing of sampling at SFU Visit. Comment column removed. - Updated definitions of analysis sets, including deletion of Full Analysis Set (FAS) and addition of Anti-drug Antibody Set (ADAS). - Added text omitted in error from original version of protocol. - Updated planned analyses. Updated vital signs information. - Clarification of study parts. - Updated planned analyses. - Updated terminology. - Clarification of definitions. - Noted that further details were provided in statistical analysis plan (SAP). - Clarified text for addition of dose level based on emerging data. - Added coagulation parameters as a row. Deleted coagulation tests from other Screening tests row. Changed “Other Screening Tests” to “Other Tests). Blood urea nitrogen (BUN) or urea creatinine changed to BUN or urea Added serum creatinine. - Added coagulation to abnormal laboratory test results bullet for events meeting the AE definition.

11 Jun 2020

Protocol Amendment 1 was dated 11-Jun-2020: - Aligned text to be consistent with Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) guidelines and to the eCRF mapping of terms. - Added activated partial thromboplastin time (aPTT), international normalized ratio (INR), and prothrombin time (PT) to list of abbreviations. - Correction of spelling, grammar, or typographical errors.

12 Oct 2020

Protocol Amendment 2 was dated 12-Oct-2020: - Separated the terms “phosphorus or phosphate” and “albumin”. - Section was restructured to clarify situations of: • participant discontinuation • treatment discontinuation • study/site discontinuation by sponsor. - Added language to Criterion clarifying that the presence of liver metastases must be recorded in the eCRF. - • Added language allowing palliative bone-directed radiotherapy as concomitant treatment • Defined taking prohibited medications as defined elsewhere in the protocol as a criterion for discontinuation of study medication. - Overall survival (OS) was originally measured from date of study enrollment to date of death. Revised to measure OS from the date of first dosing to date of death. - Excepted palliative bone-directed radiotherapy from criteria for discontinuation Added Criterion. - Added language allowing temporary suspension of study medication for up to 3 weeks. – Added clarification that site was attempt to contact participants who withdraw from the study to complete the SFU and Final Visits. - Added a section on Coronavirus Disease 2019 (COVID-19) Pandemic. - Added language regarding collection of AEs and SAEs related to COVID-19. - Replaced “early discontinuation visit” with “Safety Follow-up Visit” when specifying follow-up for positive pregnancy test. -Added language regarding missing doses due to the COVID-19 Pandemic. - In Amendment 1, the Summary of Changes table footnote reference to Cycle 1 Day 15/16 was deleted. - Footnote was added to the coagulation and ECOG assessments on Cycle 1 Day 15/16.

12 Oct 2020

Protocol Amendment 2 was dated 12-Oct-2020: - Flexibility in assessment collection for PK sampling and Screening procedures to accommodate potential impacts of the COVID-19 pandemic. - Added survival census to SFU Visit. - Added language to footnote clarifying survival census at SFU Visit. Added language to Footnote allowing collection of laboratory tests from local laboratories. - Added language to footnote expanding window of PK assessments scheduled for Day 16 to Day 21 in context of COVID-19. - Language added to define screen failures due to impacts of the COVID-19 pandemic. - Language added to define screen failures due to impacts of the COVID-19 pandemic. Exclusion Criterion was modified to remove separate conditions for study participants with bone metastases.

07 Jan 2021

Protocol Amendment 3 was dated 07-Jan-2021: - Corrected 24h Rapid Response Helpline phone number. - Added text pertaining to dose escalation (combination therapy) modules Part B and Part C throughout the document,including the synopsis, objectives and endpoints, schema, schedules of activities, background, design, benefi t-risk assessment, dose selection, selection and withdrawal criteria, treatments administered, concomitant medications, dose modifi cations, and statistical analyses. - Clarifi cation of available literature on expression data in tumors. - For better clarity, separated objectives and endpoints for Part A, A1, B, and C to 2 separate tables,one for Parts A and A1, and a second for Part B and C. Updated objectives and endpoints for Parts A and A1, and Parts B and C. Updated objectives and endpoints for Parts D, E, F, and G. - Updated Figure to reflect changes to terminology in overall design. - Added text clarifying types of tumors selected for Part A. - Exclusion criterion renumbered. Text was corrected from: “In the presence of therapeutic intent to anticoagulate the participant:INR or PT and aPTT…” to “In the presence of therapeutic intent to anticoagulate the participant: INR or PT or aPTT…” - Updated dose formulation row to clarify formulation. - Moved text and table pertaining to PK analyses. -Added text specifying which PK concentrations disclosed on public registries for Part A, Part B, and Part C. - Correction of spelling, grammar, or typographical errors.

17 Jun 2021

Protocol Amendment 4 was dated 17-Jun-2021: - Addition of the IND number. - Pharmacodynamic endpoint related to protein marker levels was updated as follows: “Change in protein marker levels in blood by scheduled assessment and dose level”. - Update of the definition of DLTs to confirm that they include any AE at least possibly related to the study medication and fulfilling the specified criteria. - Revision of the DLT definition for Part A (update of the febrile neutropenia definition as per CTCAE v5.0 and addition of Grade 4 thrombocytopenia). - Revision of the DLT definition for Part B and Part C (addition of any Grade 4 thrombocytopenia). - Revision of the eligibility criteria such that participants with locally advanced disease must also had unresectable disease (definition of the study population; Part A: inclusion criterion; Part B and Part C: inclusion criterion. The precision was also added throughout the text when relevant. The sentence at the end, which mentioned that inclusion criteria for Parts A1, B, C, D, E, F, and G defined in a protocol amendment, was moved at the end; reference to Parts B and C was deleted. - Inclusion of ramucirumab as an option in the prior treatment regimen in Part B. Revision of the eligibility criteria to provide a single QTc cutoff , irrespective of the participant’s sex (Part A: exclusion criterion, Part B: exclusion criterion, Part C: inclusion criterion). The sentence at the end, which mentioned that exclusion criteria for Parts A1, B, C, D, E, F, and G was defined in a protocol amendment, was moved at the end of; reference to Parts B and C was deleted. - Clarification that all participants with known hypersensitivity to any of the study medications excluded from the study.

17 Jun 2021

Protocol Amendment 4 was dated 17-Jun-2021: - Alignment with the UK prescribing information for oxaliplatin regarding the threshold for neutrophil count in exclusion criterion. Alignment with the UK prescribing information for calcium folinate regarding known or suspected pernicious anemia or other anemias due to vitamin B12 deficiency. - Clarification that the following should be avoided in Part C: • Concomitant administration of medicinal product with a known potential to prolong the QT interval • Concurrent administration of 5-fluorouracil and Cytochrome P450 2C9 (CYP2C9) substrates • Co-administration of medicinal products known to be nephrotoxic. Title and text modified to remove the information pertaining only to Part C of the study. All the information applying to Part C was copied or moved to a new section Prohibited concomitant treatments (medications and therapies) during Part C. - Text was corrected as follows: “Administration of live (including attenuated) vaccines was not allowed during the conduct of the study and for up to 3 months after the final dose of IMP. Administration of inactivated non-live vaccines was allowed during the study at the discretion of the Investigator.” - Deletion of the following sentence: “For participants who experience a DLT, dose adjustments were permitted if it was considered in the best interest of the participant to continue therapy at the discretion of the investigator, in consultation with the Sponsor.” - Addition of any Grade 4 nonhematologic toxicity, including diarrhea and mucositis, which was at least possibly related to UCB6114 in the list of events leading to treatment discontinuation. - Clarification that prior approval of a substantial amendment by the regulatory authorities was required for any study restart after defined stopping criteria was met.

17 Jun 2021

Protocol Amendment 4 was dated 17-Jun-2021: - Revision of the maximum amount of blood collected from each participant at Screening, during Cycle 1 and Cycle 2, and at SFU. Blood sample for pregnancy test was moved to the footnote of the table. - Update of the text to specify that liver specific alkaline phosphatase (ALP) must be separated and used to assess the liver function instead of total ALP in participants with bone metastases and liver abnormalities considered as potential Hy’s low cases. Update of Footnote. - Text pertaining to immunogenicity sampling was moved from Pharmacokinetics to the Immunogenicity. - Deletion of the following sentence: “Samples for analysis of circulating markers of bone turnover was not obtained in Part B or Part C” which was incorrect. Deletion of the related footnote in the Schedule of Activities’ tables. - Addition of the echocardiogram assessments in the study procedures for Part B and Part C to be in line with the assessments planned. Addition of collection time-windows for blood PK sampling for Part B and Part C. Update in the time schedule of the vital sign measurements on Day 1 (2h [+1h] and 5h+ [1h] after the end of infusion). - Update the contraceptive requirements for males in Parts B and C in relation to sperm donation and pregnant or breastfeeding partners (6months compared to 3 months in Part A). Addition of the recommendation to use a barrier contraceptive in addition to the use of hormonal contraceptive for woman of childbearing potential receiving Lonsurf® in the body text. Clarification that effective contraceptive method should be utilized for at last 6 months for participant in Parts B and C (compared to 3 months in Part A).

17 Jun 2021

Protocol Amendment 4 was dated 17-Jun-2021: - Correction of a few typographical and formatting errors, deletion of footnote which was not applicable for a specific assessment [Part A], footnote for “Blood collection for genetic analysis”), and addition of an existing footnote to 2 of the current procedures [Part B] and [Part C] footnote added to Eligibility criteria and Medical history as they were not assessed in Cycle 2). - Clarification in the use of "cohort" and "dose level" for Part B and Part C. - Clarification in the schematic representation of the dose escalation/DLT assessment period: • “Cohort” replaced by “dose level”, • Addition of the possibility of dose de-escalation • Clarification that each dose level could include more than one cohort of participants. - The wording “Health Authorities” was replaced by “regulatory authorities”. Correction of a few typographical and formatting errors.

14 Jan 2022

Protocol Amendment 5 was dated 14-Jan-2022: - Addition of text pertaining to dose optimization module Part A1 throughout the document, including the synopsis, objectives and endpoints, schema, schedules of activities, background, design, benefit-risk assessment, dose selection, selection and withdrawal criteria, treatments administered, concomitant medications, dose modifications, study assessments and procedures, statistical analyses, and appendices. When applicable, sections, tables and figures was renumbered. - Part A1 ‘dose adaptation module’ was renamed ‘dose optimization module’ for clarity. - In secondary and tertiary endpoints, the wording ‘dose level’ was replaced by ‘cohort’ to cover both dose level in Part A and dosing schedule in Part A1. The changes were also applied throughout the document, where relevant. - The description of the Safety Monitoring Committee (SMC) and Study Steering Committee (SSC) were applicable for all study parts; thus, the information was moved up in a separate section. Subsequent sections was renumbered. Treatment duration text was updated to include “criteria for discontinuation were met”, in line with the text provided in the study synopsis (new text in bold). - The rationale for indication for Part B and Part C was the same as for Part A1 and the corresponding text was moved. It was clarified that Ab7326mIgG1 is the murinized version of UCB6114. - A correction was made in the exclusion criteria for Part A, Part B and Part C: “Screening of asymptomatic participants without history of central nervous system (CNS) metastases was not required”. - Clarification that death due to disease progression was not be recorded as a SAE but was recorded in a survival electronic case report form (eCRF). -Clarifications of the procedures to be performed in case an infusion-related reaction occurs. - Clarification that a SAP were developed for each module.

14 Jan 2022

Protocol Amendment 5 was dated 14-Jan-2022: - Timepoints at which the duration of responses and Progression-free survival (PFS) was derived was corrected to be in line with the statistical analysis plan. - Correction of spelling, grammar, or typographical errors. - Type of amendment for protocol amendment 3.1 was changed from ‘substantial’ to ‘Not applicable’ as the substantial/non substantial classification was irrelevant in United States (US).

26 Jun 2023

Protocol Amendment 6 was dated 26-Jun-2023: - Clarification that either the entire study or an individual Study Part could be suspended. Clarification of the process for study/individual Study Part hold/potential restart when criteria for study/individual Study Part suspension were met. - Footnotes of (Part A1, Cohort 3) was updated to clarify when blood sample for PK and Gremlin should be collected with regards to biopsy. Footnotes (Part B) and (Part C) was updated to clarify when blood samples for ADA, circulating gremlin-1 and ctDNA analysis to be collected. In line with this change, footnote was added. - Correction of typographical errors.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
10 May 2023	A temporary hold was implemented in ONC001 Study Part C to investigate a fatal serious adverse event (SAE) reported in one study participant enrolled in Part C of the Phase 1/2 first-in-human (FIH) study ONC001, where ginisortamab (UCB6114) is administered in combination with modified FOLFOX6 (mFOLFOX6; 5 fluorouracil [5-FU], leucovorin, and oxaliplatin). Investigation and new information did not support a role of ginisortamab (UCB6114) in cause of death. Health authorities were notified on 26 June 2023 to restart enrollment and dosing of ginisortamab in ONC001 Part C.	11 Jul 2023

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

None reported

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A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

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Clinical Trial Results: A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

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A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors